Genetics and Health

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Chapter 4
Genetics and Health

Even at birth the whole individual is destined to die, and perhaps his organic disposition may already contain the indication of what he is to die from.

Sigmund Freud, 1924

Genetics, which is the branch of biology that studies heredity, concerns the biochemical instructions that convey information from generation to generation. In order to appreciate the role of genetics in health and illness, it is important to understand the interaction of genes, chromosomes, and genomes and to learn how deoxyribonucleic acid (DNA) functions as the information molecule of living organisms.

Genes are units of hereditary information that are made of DNA and located on chromosomes, which are separate strands of DNA wrapped in a double helix (two intertwined three-dimensional spirals) around a core of proteins contained in the nuclei of cells. Genes contain the instructions for the production of proteins, which make up the structure of cells and direct their activities. They exist in corresponding pairs, and a genome is a complete set of paired genes for an organism. Humans have 46 chromosomes arranged in 23 pairs, and the human genome contains about 30,000 genes and 600,000 pairs of DNA. Changes in the number, size, shape, or structure of chromosomes can result in a variety of physical and mental abnormalities and diseases.


For inheritance of simple genetic traits, the two inherited copies of a gene determine the phenotype (the observable characteristic) for that trait. When genes for a particular trait exist in two or more different forms that may differ between individuals and populations, they are called alleles. For example, brown and blue eye colors are due to different alleles for eye color. For every gene, the offspring receives two alleles, one from each parent. The combination of inherited alleles is the genotype of the organism, and its expression—the observable characteristic—is its phenotype.

For many traits the phenotype is a result of an interaction between the genotype and the environment. Some of the most readily apparent traits in humans, such as height, weight, and skin color, result from interactions between genetic and environmental factors. In addition, there are complex phenotypes that involve multiple gene-encoded proteins and the alleles of these particular genes are influenced by other factors, either genetic or environmental. So while the presence of certain genes indicates susceptibility or likelihood to develop a certain trait, it does not guarantee expression of the trait.

For a specific trait, some alleles may be dominant while others are recessive. The phenotype of a dominant allele is always expressed, while the phenotype of a recessive allele is expressed only when both alleles are recessive. Recessive genes continue to pass from generation to generation, however, they are only expressed in individuals that do not inherit a copy of the dominant gene for the specific trait.

There also are some instances, known as incomplete dominance, when one allele is not completely dominant over the other, and the resulting phenotype is a blend of both traits. Skin color in humans is an example of a trait often governed by incomplete dominance, with offspring appearing to be a blend of the skin tones of each parent. Further, some traits are determined by a combination of several genes (multigenic or polygenic), and the resulting phenotype is determined by the final combination of alleles of all the genes that govern the particular trait.

Some multigenic traits are governed by many genes, and each contributes equally to the expression of the trait. In such instances, a defect in a single gene pair may not have a significant impact on expression of the trait. Other multigenic traits are predominantly directed by one major gene pair and only mildly influenced by the effects of other gene pairs. For these traits, the impact of a defective gene pair depends on whether it is the major pair governing expression of the trait or one of the minor pairs influencing its expression.

A range of other factors enters into whether a trait will be evidenced and the extent to which it is expressed. For example, different individuals may express a trait with different levels of severity. This phenomenon is known as variable expressivity.

The Influence of Heredity on Health

It has long been known that heredity affects health. Genetics explains how and why certain traits such as hair color and blood types run in families. Genomics, a discipline that is only about two decades old, is the study of more than single genes; it considers the functions and interactions of all the genes in the genome. In terms of health and disease, genomics has a broader and more promising range than does genetics. The science of geno-mics relies on knowledge of and access to the entire genome and applies to common conditions, such as breast and colorectal cancer, Parkinson's disease, and Alzheimer's disease. It also has a role in infectious diseases once believed to be entirely environmentally caused, such as human immunodeficiency virus (HIV, which is the virus that causes acquired immune deficiency syndrome [AIDS]) infection and tuberculosis. Like most diseases, these frequently occurring disorders are due to the interactions of multiple genes and environmental factors. Genetic variations in these disorders may have a protective or a causative role in the expression of diseases.

It is commonly accepted that diseases fall into one of three broad categories: those few that are primarily genetic in origin, disorders that are largely attributable to environmental causes, and the majority of conditions in which genetics and environmental factors make important, though not necessarily equal, contributions. As understanding of genomics advances and scientists identify genes involved in more diseases, the distinction between these three classes of disorders is diminishing. This chapter considers genetic testing, some of the disorders believed to be predominantly genetic in origin, and some that are the result of genes acted on by environmental factors.


There are two types of genes: dominant and recessive. When a dominant gene is passed on to offspring, the feature or trait it determines will appear regardless of the characteristics of the corresponding gene on the chromosome inherited from the other parent. If the gene is recessive, the feature it determines will not show up in the offspring unless both the parents' chromosomes contain the recessive gene for that characteristic. Similarly, among diseases and conditions primarily attributable to a gene or genes, there are autosomal (a non-sex-related chromosome) dominant disorders and autosomal recessive disorders.

Another way to characterize genetic disorders is by their pattern of inheritance, as single gene, multifactorial, chromosomal, or mitochondrial. Single-gene disorders (also called Mendelian or monogenic) are caused by mutations in the deoxyribonucleic acid (DNA) sequence of one gene. There are more than six thousand known single-gene disorders, which, according to the U.S. National Library of Medicine (, occur in about one in every two hundred births. Examples are cystic fibrosis, sickle cell anemia, Huntington's disease, and hereditary hemochromatosis. Hemochromatosis is a disorder in which the body absorbs too much iron from food. Rather than the excess iron being excreted, it is stored throughout the body, and iron deposits damage the pancreas, liver, skin, and other tissues. Single-gene disorders are the result of either autosomal dominant, autosomal recessive, or X-linked inheritance (involving a gene on the X chromosome passed down through the family).

Multifactorial or polygenic disorders result from a complex combination of environmental factors and mutations in multiple genes. For example, different genes that influence breast cancer susceptibility have been found on seven different chromosomes, rendering it more difficult to analyze than single-gene or chromosomal disorders. Some of the most common chronic diseases are multi-factorial in origin. Examples include heart disease, Alzheimer's disease, arthritis, diabetes, and cancer.

Chromosomal disorders are produced by abnormalities in chromosome structure, missing or extra copies of chromosomes, or errors such as translocations (movement of a chromosome section from one chromosome to another). Down syndrome is a chromosomal disorder that results when an individual has an extra copy, or a total of three copies, of chromosome 21. Mitochondrial disorders result from mutations in the nonchromosomal DNA of mitochondria, which are organelles involved in cellular respiration. Compared with the three other patterns of inheritance, mitochondrial disorders occur infrequently.

At the dawn of the twenty-first century, the possibility of preventing and changing genetic legacies appears within reach of modern medical science. Genomic medicine predicts the risk of disease in the individual, whether highly probable as in the case of some of the well-established single-gene disorders, or in terms of an increased susceptibility likely to be influenced by environmental factors. The promise of genomic medicine is to

make preventive medicine more powerful and treatment more specific to the individual, enabling investigation and treatment that are custom-tailored to an individual's genetic susceptibilities, or to the characteristics of the specific disease or disorder.


A genetic test is the analysis of human DNA, ribonucleic acid (RNA), chromosomes, and proteins in order to detect heritable diseases for the purposes of diagnosis, treatment, and other clinical decision making. Most genetic testing is performed by drawing a blood sample and extracting DNA from white blood cells. There is a broad range of techniques that can be used for genetic testing. Genetic tests have diverse purposes, including screening for and diagnosis of genetic disease in newborns, children, and adults; the identification of future health risks; the prediction of drug responses; and the assessment of risks to future offspring.

There is a difference between genetic tests performed to screen for disease and testing conducted to establish a diagnosis. Diagnostic tests are intended to definitively determine whether a patient has a particular problem. Diagnostic tests are generally complex tests and commonly require sophisticated analysis and interpretation. They may be expensive and are generally performed only on persons believed to be "at risk," such as patients who already have symptoms of a specific disease.

In contrast, screening is performed on healthy, asymptomatic (showing no symptoms of disease) people and often to the entire relevant population. A good screening test is relatively inexpensive, easy to use and interpret, and assists to identify which individuals in the population are at higher risk for a specific disease. By definition, screening tests identify persons who need further testing or persons who should take special preventive measures or precautions. For example, persons deemed especially susceptible to genetic conditions with specific environmental triggers are advised to avoid the environmental factors linked to developing the disease.

Examples of genetic tests used to screen relevant populations include screening persons of Ashkenazi Jewish heritage (the east European Jewish population primarily from Germany, Poland, and Russia, as opposed to the Sephardic Jewish population primarily from Spain, parts of France, Italy, and North Africa) for Tay-Sachs disease, African-Americans for sickle cell disease, and expectant mothers over age thirty-five whose fetuses are at higher risk for Down syndrome. Table 4.1 lists a few of the more than one thousand DNA-based genetic tests that are currently available.

The most common form of genetic testing is screening of newborn infants for genetic abnormalities. In the


Currently available DNA-based gene tests

Alpha-1-antitrypsin deficiency (AAT; emphysema and liver disease)

Amyotrophic lateral sclerosis (ALS; Lou Gehrig's Disease; progressive motor function loss leading to paralysis and death)

Alzheimer's disease (APOE; late-onset variety of senile dementia)

Ataxia telangiectasia (AT; progressive brain disorder resulting in loss of muscle control and cancers)

Gaucher disease (GD; enlarged liver and spleen, bone degeneration)

Inherited breast and ovarian cancer (BRCA 1 and 2; early-onset tumors of breasts and ovaries)

Hereditary nonpolyposis colon cancer (CA; early-onset tumors of colon and sometimes other organs)

Charcot-Marie-Tooth (CMT; loss of feeling in ends of limbs)

Congenital adrenal hyperplasia (CAH; hormone deficiency; ambiguous genitalia and male pseudohermaphroditism)

Cystic fibrosis (CF; disease of lung and pancreas resulting in thick mucous accumulations and chronic infections)

Duchenne muscular dystrophy/Becker muscular dystrophy (DMD; severe to mild muscle wasting, deterioration, weakness)

Dystonia (DYT; muscle rigidity, repetitive twisting movements)

Fanconi anemia, group C (FA; anemia, leukemia, skeletal deformities)

Factor V-Leiden (FVL; blood-clotting disorder)

Fragile X syndrome (FRAX; leading cause of inherited mental retardation)

Hemophilia A and B (HEMA and HEMB; bleeding disorders)

Hereditary hemochromatosis (HFE; excess iron storage disorder)

Huntington's disease (HD; usually midlife onset; progressive, lethal, degenerative neurological disease)

Myotonic dystrophy (MD; progressive muscle weakness; most common form of adult muscular dystrophy)

Neurofibromatosis type 1 (NF1; multiple benign nervous system tumors that can be disfiguring; cancers)

Phenylketonuria (PKU; progressive mental retardation due to missing enzyme; correctable by diet)

Adult polycystic kidney disease (APKD; kidney failure and liver disease)

PraderWilli/Angelman syndromes (PW/A; decreased motor skills, cognitive impairment, early death)

Sickle cell disease (SS; blood cell disorder; chronic pain and infections)

Spinocerebellarataxia, type 1 (SCA1; involuntary muscle movements, reflex disorders, explosive speech)

Spinal muscular atrophy (SMA; severe, usually lethal progressive muscle-wasting disorder in children)

Thalassemias (THAL; anemias—reduced red blood cell levels)

Tay-Sachs disease (TS; fatal neurological disease of early childhood; seizures, paralysis)

source: "Some Currently Available DNA-Based Gene Tests," in "Gene Testing," U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research, Human Genome Program, Human Genome Project Information, (accessed December 29, 2005)

United States, according to a 2003 report by the Government Accountability Office, about four million newborns per year are screened by testing blood obtained from a prick of the newborn's heel within the first few days of life. Specific genetic disorders such as phenylketonuria (PKU), an inherited error of metabolism resulting from a deficiency of an enzyme called phenylalanine hydroxylase, can be identified with heel-prick testing. The lack of this enzyme can produce mental retardation, organ damage, and postural problems. Children born with PKU must pay close attention to their diets so that they may lead healthy, normal lives.

Genetic screening is intended to identify disorders that require early detection and treatment to prevent serious illness or death. Each state determines which disorders to include in its screening program; the number chosen ranges from four to thirty-six, with eight or

less being the most common. Table 4.2 shows the disorders frequently included in screening programs and how many states require each. To help determine which disorders to screen for, states generally consider criteria such as how often the disorder occurs in the population, whether an effective screening test exists, and whether the disorder is treatable. Table 4.3 shows the national

Disorders most commonly included in state newborn screening programs
DisorderNumber of states*
Note: This table does not include states that provide screening for the disorders to selected populations, as part of pilot programs, or by request.
*"States" refers to the 50 states and the District of Columbia.
source: "Table 1. Disorders Most Commonly Included in State Newborn Screening Programs, December 2002," in Newborn Screening: Characteristics of State Programs, U.S. General Accounting Office, March 2003, (accessed December 15, 2005)
Phenylketonuria (PKU)51
Congenital hypothyroidism51
Sickle cell disease44
Congenital adrenal hyperplasia32
Biotinidase deficiency24
Maple syrup urine disease24
Information on disorders most commonly included in state newborn screening programs
DisorderNational incidence, 1990–99DescriptionPotential outcomesTreatment
source: "Appendix III. Information on Disorders Most Commonly Included in State Newborn Screening Programs," in Newborn Screening: Characteristics of State Programs, U.S. General Accounting Office, March 2003, (accessed December 15, 2005)
Phenylketonuria1 in 13,947Deficiency of an enzyme needed to break down the amino acid phenylalanineMental retardation, seizuresLow-phenylalanine diet
Congenital hypothyroidism1 in 3,044Inability to produce adequate amount of thyroid hormoneMental retardation, stunted growthThyroid hormone
Galactosemia1 in 53,261Deficiency of an enzyme needed to break down the milk sugar galactoseBrain damage, liver damage, cataracts, deathGalactose-free diet
Sickle cell diseases
    Sickle cell anemia1 in 3,721Inherited blood disorder causing hemoglobin abnormalitiesOrgan damage, delayed growth, strokePenicillin, vaccinations
    Hemoglobin sickle C disease1 in 7,386
Congenital adrenal hyperplasia1 in 18,987Deficiency of an adrenal enzyme needed to produce cortisol and aldosteroneDeath due to salt loss, reproductive and growth difficultiesHormone replacement and salt replacement
Biotinidase deficiency1 in 61,319Deficiency of the enzyme biotinidase, needed to recycle the vitamin biotinMental retardation, developmental delay, seizures, hearing lossBiotin supplements
Maple syrup urine disease1 in 230,028Deficiency of the enzyme needed to metabolize leucine, isoleucine, andvalineMental retardation, seizures, coma, deathDietary management and supplements
Homocystinuria1 in 343,650Deficiency of the enzyme needed to metabolize the amino acid homocysteineMental retardation, eye problems, skeletal abnormalities, strokeDietary management and vitamin supplements

incidence, potential outcomes, disorder.


There are thousands of genetic diseases, such as sickle cell anemia, cystic fibrosis, and Tay-Sachs disease, that may be passed from one generation to the next. Numerous tests have been developed to help screen parents at risk of passing on genetic disease to their children as well as to identify embryos, fetuses, and newborns that suffer from genetic diseases.

Carrier Identification

Carrier identification is the term for genetic testing to determine whether a healthy individual has a gene that may cause disease if passed on to his or her offspring. It is usually performed on people considered to be at higher than average risk, such as those of Ashkenazi Jewish descent, who have a one in thirty chance of being Tay-Sachs disease carriers (in other populations the risk is about one in three hundred). Testing is necessary because many carriers have just one copy of a gene for an autosomal recessive trait and are unaffected by the trait or disorder. Only someone with two copies of the gene will actually have the disorder. So while it is widely assumed that everyone is an unaffected carrier of at least one autosomal recessive gene, it only presents a problem in terms of inheritance when two parents have the same recessive disorder gene (or both are carriers). In this instance the offspring would each have a one in four chance of receiving a defective copy of the gene from each parent and developing the disorder.

Another example of carrier identification is the test for a deletion in the dystrophin gene, which results in Duchenne muscular dystrophy. Carriers may avoid having an affected child by preventing pregnancy or by undergoing prenatal testing for Duchenne muscular dystrophy, with the option of ending the pregnancy if the fetus is found to be affected.

Using genetic testing to detect carriers poses some challenges. Typically, a carrier has inherited a mutant gene from one parent and a normal gene from another parent. If, however, the carrier harbors a mutation that is only found in germ cells (the sperm or eggs), and only in some of these germ cells, then conventional genetic testing, which is performed on white blood cells, will miss the mutation.

Preimplantation Genetic Diagnosis

Preimplantation genetic diagnosis (PGD) is a newer genetic test that enables parents undergoing in vitro fertilization (fertilization that takes place outside the body) to screen an embryo for specific genetic mutations when it is no larger than six or eight cells and before it is implanted in the uterus to grow and develop. One advantage of PGD is that it can screen any congenital disorder for which the causative gene is known and may be used by couples that wish to avoid traditional prenatal diagnosis and the possibility of termination of pregnancy.

Prenatal Testing

Prenatal genetic testing enables physicians to diagnose diseases in the fetus. Most genetic tests examine blood or other tissue from the mother to detect abnormalities. An example of a blood test is the triple marker screen. This test measures levels of alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol, and can identify some birth defects such as Down syndrome and neural tube defects. (Two of the most common neural tube defects are anencephaly—absence of the majority of the brain—and spina bifida—incomplete development of the back and spine). Triple marker screen results are usually available within several days, and women with abnormal results are often advised to undergo additional diagnostic testing such as chorionic villus sampling (CVS), amniocentesis, or percutaneous umbilical blood sampling (withdrawing blood from the umbilical cord).

CVS enables obstetricians and perinatologists (physicians specializing in evaluation and care of high-risk expectant mothers and infants) to assess the progress of pregnancy during the first trimester (the first three months). The optimal time for CVS is between ten and eleven and a half weeks of gestation. The cells obtained via CVS are examined in the laboratory for indications of genetic disorders such as cystic fibrosis, Down syndrome, Tay-Sachs disease, and thalassemia, and the results of testing are available within seven to fourteen days. CVS provides the same diagnostic information as amniocentesis; however, the risks (miscarriage, infection, vaginal bleeding, and birth defects) associated with CVS are slightly higher. Approximately one in every one hundred pregnancies is miscarried as a result of CVS.

Amniocentesis involves taking a sample of the fluid that surrounds the fetus in the uterus for chromosome analysis. An amniocentesis is usually performed at fifteen to eighteen weeks of gestation, although it can be done as early as twelve weeks. Like CVS, amniocentesis samples and analyzes cells derived from the baby to enable parents to learn of chromosomal abnormalities, as well as the gender of the unborn child, about two weeks after the test is performed. The risk of miscarriage—about one in every two hundred pregnancies—resulting from amniocentesis is lower than the risk associated with CVS.

Using samples of genetic material obtained from amniocentesis or CVS, physicians can detect disease in an unborn child. Down syndrome (also known as trisomy 21, because it is caused by an extra copy of chromosome 21) is the genetic disease most often identified using this technique. Down syndrome is rarely inherited; most cases result from an error in the formation of the ovum (egg) or sperm, leading to the inclusion of an extra chromosome 21 at conception. As with prenatal diagnosis for most inherited genetic diseases, this use of genetic testing is focused on reproductive decision making.

The most invasive prenatal procedure for genetic testing is percutaneous umbilical blood sampling. Under high-resolution ultrasound, a sample of fetal blood is removed from the umbilical cord. This test can be performed from approximately sixteen weeks gestation to term. Percutaneous umbilical blood sampling poses the greatest risk to the unborn child—one in fifty miscarriages occur as a result of this procedure. It is used when a diagnosis must be made quickly. For example, when an expectant mother is exposed to an infectious agent with the potential to produce birth defects, it may be used to examine fetal blood for the presence of infection.


Genetic testing also can be performed postnatally (after birth) to determine which children and adults are at increased risk of developing specific diseases. Scientists can perform predictive genetic testing to identify which individuals are at risk for cystic fibrosis, Tay-Sachs disease, Huntington's disease, amyotrophic lateral sclerosis (ALS; a degenerative neurologic condition commonly known as Lou Gehrig's disease), and several types of cancers (including some cases of breast, colon, and ovarian cancer).

A positive test result (the presence of a defective or altered gene) from predictive genetic testing does not guarantee that the individual will develop the disease; it simply identifies the individual as genetically susceptible and at increased risk for developing the disease. For example, a woman who tests positive for the BRCA1 gene has about an 80% chance of developing breast cancer before age sixty-five. It is also important to note that like other types of diagnostic medical testing, genetic tests are not 100% predictive—the results rely on the quality of laboratory procedures and accuracy of interpretations. Further, because tests vary in their sensitivity and specificity, there is always the possibility of false-positive and false-negative test results.

Researchers hope that positive test results will encourage people at higher-than-average risk of developing a disease to be especially vigilant about disease prevention and screening to detect the disease early, when it is most successfully treated. There is an expectation that genetic information will increasingly be used in routine population screening to determine individual susceptibility to common disorders such as heart disease, diabetes, and cancer. Such screening will identify groups at risk so that primary prevention efforts such as diet and exercise or secondary prevention efforts such as early detection can be initiated.

Symptomatic Genetic Testing

Most genetic testing is performed on persons who are asymptomatic to determine if they are carriers or to identify susceptibility or risk of developing a specific disease or disorder. There is, however, some testing performed on persons with symptoms of a disease in order to clarify or establish the diagnosis and calculate the risk of developing the disease for other family members. This type of testing is known as diagnostic genetic testing, predictive genetic testing, or symptomatic genetic testing. It determines the likelihood that a healthy person with a family history of a disorder will develop the disease. Testing positive for a specific genetic mutation indicates an increased susceptibility to the disorder but does not establish the diagnosis. For example, a woman may choose to undergo testing to find out whether she has genetic mutations that would indicate the likelihood of developing hereditary cancer of the breast or ovary (BRCA1 and BRCA2, respectively). If she tests positive for the genetic mutation, she may then decide to undergo some form of preventive treatment. Preventive measures may include increased surveillance such as more frequent mammography, chemoprevention—prescription drug therapy intended to reduce risk—or surgical prophylaxis, such as mastectomy (surgical removal of one or both breasts) and/or oophorectomy (surgical removal of one or both ovaries).

This type of testing also may assist in directing treatment for symptomatic patients in whom a mutation in a single gene (or in a gene pair) accounts for a disorder. Cystic fibrosis and myotonic dystrophy (the most common adult form of muscular dystrophy) are examples of disorders that may be confirmed or ruled out by diagnostic genetic testing and other methods (the sweat test for cystic fibrosis, see below, or a neurologic evaluation for myotonic dystrophy).

One issue involved in symptomatic genetic testing is the appropriate frequency of testing in view of rapidly expanding genetic knowledge and identification of genes linked to disease. Physicians frequently see symptomatic patients for whom there is neither a definitive diagnosis nor a genetic test. The as yet unanswered question is: should such persons be recalled for genetic testing each time a new test becomes available? Although clinics that perform genetic testing counsel patients to maintain regular contact so they may learn about the availability of new tests, there is no uniform guideline or recommendation about the frequency of testing.

Testing Children for Adult-Onset Disorders

In 2000 the American Academy of Pediatrics Committee on Genetics recommended genetic testing for persons under age eighteen only when testing offers immediate medical benefits or when there is a benefit to another family member and there is no anticipated harm to the person being tested. The committee considered genetic counseling before and after testing as essential components of the process (Muin J. Khoury et al, "Population Screening in the Age of Genomic Medicine," 2003,

The American Academy of Pediatrics Committee on Bioethics and Newborn Screening Task Force recommended that genetic tests included in the newborn-screening battery should be based on scientific evidence. The academy also advocated informed consent for newborn screening. (To date, the majority of states do not require informed consent.) The Committee on Bioethics did not endorse carrier screening in persons less than eighteen years of age, except in the case of a pregnant teenager. It also recommended against predictive testing for adult-onset disorders in persons under eighteen years.

The American College of Medical Genetics, the American Society of Human Genetics, and the World Health Organization have also weighed in about genetic testing of asymptomatic children, asserting that decision making should emphasize the child's well-being. One issue involves the value of testing of asymptomatic children for genetic mutations associated with adult-onset conditions such as Huntington's disease. Because no treatment can be begun until the onset of the disease, and presently there is no treatment to alter the course of the disease, it may be ill advised to test for it. Another concern is testing for carrier status of autosomal-recessive or X-linked conditions such as cystic fibrosis or Duchenne muscular dystrophy. Experts caution that children might confuse carrier-status with actually having the condition, which in turn might provoke needless anxiety.

There are, however, circumstances in which genetic testing of children may be appropriate and useful. Examples are children with symptoms of suspected hereditary disorders or those at risk for cancers in which inheritance plays a primary role. In "Genetic Testing and Screening" (American Journal of Nursing, vol. 102, no. 7, July 2002), Dale Halsey Lea and Janet Williams cite children with a family history of familial adenomatous polyposis (FAP) and those diagnosed with certain childhood cancers, such as multiple endocrine neoplasia, as appropriate candidates for genetic testing. They observe that testing can assist to determine planning, surveillance, and treatment for those who are found to have the FAP genetic mutation. Genetic testing for certain childhood cancers may serve to predict risk and improve detection of subsequent malignancies. Lea and Williams concur that the child must agree to and understand the function of genetic testing, and they reiterate that to administer genetic testing to a child not only requires parental consent but also the child's consent.

New Testing Guidelines for Infants Sparks Debate

In the article "Panel to Advise Testing Babies for 29 Diseases" in the February 21, 2005, issue of The New York Times (, Gina Kolata reports that a federal advisory group recommendation advocating screening infants for twenty-nine rare medical conditions has generated debate among health care professionals and the general population. The advisory group not only seeks to expand newborn screening but also to standardize it from state to state. In 2005 some states screened for just four conditions while others test newborns for as many as thirty-five diseases.

Advocates of expanded newborn screening assert that while the twenty-nine conditions occur infrequently, there are effective, potentially lifesaving medical treatments for each condition. Opponents claim that the efficacy of treatment has not been adequately evaluated or substantiated. They further caution that screening detects even those infants with the mildest forms of the disorders and essentially forces parents and health care professionals to consider treatment that may be more harmful than the mild disorder. They also wonder about the advisability of labeling infants with diagnoses of diseases from which they may never suffer.


Rapid advances in genetic research during the past two decades have challenged scientists, health care professionals, ethicists, government regulators, legislators, and consumers to stay abreast of new developments. Understanding the scientific advances and their implications is critical for everyone involved in making informed decisions about the ways in which genetic research and information will affect the lives of current and future generations. The pivotal importance of these societal decisions was underscored by the allocation of 5% of the budget of the Human Genome Project for the study of ethical, legal, and social issues related to genetic research. (The Human Genome Project was a thirteen-year study completed in 2003 conducted by the U.S. Department of Energy and the National Institutes of Health [NIH] that set out to, among other things, identify all of the genes in human DNA.) To date, consideration of these ethical issues has not produced simple or universally applicable answers to the many questions posed by the increasing availability of genetic information. Ongoing public discussion and debate are intended to inform, educate, and assist persons in every walk of life to make personal decisions about their health and participate in decisions that concern others.

As researchers learn more about the genes responsible for a variety of illnesses, they can design more tests with ever-increasing accuracy and reliability to predict whether an individual is at risk of developing specific diseases. The ethical issues involved in genetic testing have turned out to be far more complicated than originally anticipated. Initially, physicians and researchers believed that at-risk families would welcome a test to determine in advance who would develop or escape a disease. They would be able to plan more realistically about having children, choosing jobs, obtaining insurance, and living their lives. Nevertheless, many people with family histories of a genetic disease have decided that not knowing is better than anticipating a grim future and an agonizing, slow death. They prefer to live with the hope that they will not develop the disease rather than having the certain knowledge that they will.

The discovery of genetic links and the development of tests to predict the likelihood or certainty of developing a disease raise ethical questions for persons who carry a defective gene. Should women who are carriers of Huntington's disease or cystic fibrosis have children? Should a fetus with the defective gene be carried to term or aborted? Serving as an example of this issue's complexity, one health insurance company agreed to pay for prenatal cystic fibrosis testing for a mother who already had one affected child, but the company insisted if the baby was affected, the mother would have to terminate the pregnancy or it would not cover the child's future medical bills.

There are also concerns about privacy and the confidentiality of medical records, and the results of genetic testing leading to possible stigmatization. Some people are reluctant to be tested because they fear they may lose their health, life, and disability insurance, or even their jobs, if they are found to be at risk for a disease. Genetic tests are sometimes costly, and some insurers agree to reimburse for testing only if they are informed of the results. The insurance companies feel they cannot risk selling policies to people they know will become disabled or die prematurely.

The fear of discrimination by insurance companies or employers if they learn the results of genetic testing is often justified. An insurance carrier may charge someone a higher rate or disqualify an individual based on test results, and an employer might choose not to hire or to deny an affected individual a promotion. The American Society of Medical Genetics and most other medical professional associations agree that people should not be forced to choose between having a genetic test that could provide lifesaving information and avoiding a test to save a job or retain health insurance coverage.


Although many diseases, disorders, and conditions are termed "genetic," classifying a disease as genetic simply means that there is an identified genetic component to either its origin or expression. Many medical geneticists contend that the majority of diseases cannot be classified as strictly genetic or environmental. Environmental factors can greatly influence the way disease causing genes express themselves. They can even prevent the genes from being expressed at all. Similarly, environmental (infectious) diseases may not be expressed because of some genetic predisposition to immunity. Each disease, in each individual, exists along a continuum between a genetic disease and an environmental disease.

A multitude of diseases are believed to have strong genetic contributions, including:

  • Heart disease—coronary atherosclerosis, hypertension (high blood pressure), and hyperlipidemia (elevated blood levels of cholesterol and other lipids)
  • Diabetes
  • Cancer—retinoblastomas, colon, stomach, ovarian, uterine, lung, bladder, breast, skin (melanoma), pancreatic, and prostate
  • Neurological disorders—Alzheimer's disease, amyotrophic lateral sclerosis (also known as Lou Gehrig's disease), Gaucher's disease, Huntington's disease, multiple sclerosis, narcolepsy, neurofibromatosis, Parkinson's disease, Tay-Sachs disease, and Tourette's syndrome
  • Mental illnesses, mental retardation, and behavioral conditions—alcoholism, anxiety disorders, attention deficit hyperactivity disorder, eating disorders, Lesch-Nyhan syndrome, manic depression, and schizophrenia
  • Other disorders—cleft lip and cleft palate, clubfoot, cystic fibrosis, Duchenne muscular dystrophy, glucose galactose malabsorption, hemophilia, Hurler's syndrome, Marfan's syndrome, phenylketonuria, sickle cell disease, and thalassemia
  • Medical and physical conditions with genetic links—alpha-1-antitrypsin, arthritis, asthma, baldness, congenital adrenal hyperplasia, migraine headaches, obesity, periodontal disease, porphyria, and selected speech disorders

Cystic Fibrosis

Cystic fibrosis (sometimes referred to as CF) is the most common inherited fatal disease of children and young adults in the United States. According to the Merck Manual of Diagnosis and Therapy (17th edition, 1999,, it occurs in about one in every three thousand Caucasian births, one in fifteen thousand African-Americans, and one in thirty-two thousand Asian-Americans. According to the Cystic Fibrosis Foundation (, in 2006 an estimated thirty thousand young people had the disease; their median life span (half of this population were above and half were below) is thirty-seven years. An estimated twelve million Americans (one in twenty-five), almost all of whom are white, are symptomless carriers of the CF gene. Like sickle cell disease, it is a recessive genetic disorder—in order to inherit this disease, a child must receive the CF gene from both parents.

In 1989 the CF gene was identified and in 1991 it was cloned and sequenced. The gene was called cystic fibrosis transmembrane conductance regulator (CFTR) because it was discovered to encode a membrane protein that controls the transit of chloride ions across the plasma membrane of cells. Nearly one thousand mutations of the large gene have been identified. Though most are extremely rare, several account for more than two-thirds of all mutations. The mutated versions of the gene found in persons with CF were found to cause relatively modest impairment of chloride transport in cells. Chloride transport is critical because chloride is a component of salt involved in fluid absorption and volume regulation, and this seemingly minor defect can result in a multisystem disease that affects organs and tissues throughout the body, provoking abnormal, thick secretions from glands and epithelial cells. Eventually, sticky mucus fills the lungs and pancreas, causing difficulty in breathing and interference with digestion; ultimately, affected children die of respiratory failure.

At first, a child with CF does not appear to be suffering from a serious illness, but the diagnosis is usually made by the age of three. Often the only signs are a persistent cough, a large appetite but poor weight gain, an extremely salty taste to the skin, and large, foul-smelling bowel movements. A simple "sweat test" is currently the standard diagnostic test for CF. The test measures the amount of salt in the sweat; abnormally high levels are the hallmark of CF.


In August 1989 researchers isolated the specific gene that causes CF. The mutation of this gene accounts for about 70% of the cases of the disease. In 1990 scientists successfully corrected the biochemical defect by inserting a healthy gene into diseased cells grown in the laboratory, a major step toward developing new therapies for the disease. In 1992 they injected healthy genes into laboratory rats by using a deactivated common cold virus as the delivery agent. The rats began to manufacture the missing protein, which regulates the chloride and sodium in the tissues, preventing the deadly buildup of mucus. Scientists were hopeful that within a few years CF would be eliminated as a fatal disease, giving many children the chance for healthy, normal lives.

In 1993, however, optimism faded when the medical community discovered that the CF gene was more complicated than expected. Scientists found that the gene can be mutated at more than 950 points, and more points were appearing at an alarming rate. At the same time, they discovered that many people who have inherited mutated genes from both parents do not have CF. With so many possible mutations, the potential combinations in a person who inherits one gene from each parent are immeasurable.

The combinations of different mutations create different effects. Some may result in crippling and fatal CF, while others may cause less serious disorders, such as infertility, asthma, or chronic bronchitis. To further complicate the picture, other genes can alter the way different mutations of the CF gene affect the body.

In 2006 the Cystic Fibrosis Foundation continued to support clinical research studies in human gene therapy. Several studies are using the adenovirus rather than the common cold virus as the vehicle for delivering healthy genes to lung or nasal tissue. Another study is using liposomes (fat cells) as a delivery vehicle. Still another form of gene therapy uses a compacted DNA technology. The goal is for the DNA to produce the CFTR protein that is needed to correct the basic defect in CF cells.

Researchers are also finding more evidence that CF mutations may be much more common than previously thought. For example, five thousand healthy women receiving prenatal care at Kaiser Permanente in northern California were tested for the CF gene, thought to be present in less than 1% of the population. Of those screened, 11% had the mutation. This finding may indicate that many more common diseases, such as asthma, may be caused by mutations of the CF gene. Other scientists have speculated that the frequency of CF carriers among persons of European descent may have, at some point in time, conferred immunity to some other disorder, in much the same way that sickle cell carriers were found to be protected from contracting malaria.


Because there is a relatively high frequency of carriers of the defective gene in the general population, in 2000 the NIH, the American College of Medical Genetics, and the American College of Obstetricians and Gynecologists issued a recommendation that CF screening be offered to every white woman who is pregnant or considering having a baby. However, the results of several research studies have found that many people who carry the CF gene fail to inform family members about their risk ("Genetic Testing for Cystic Fibrosis: National Institutes of Health Consensus Development Conference Statement on Genetic Testing for Cystic Fibrosis," Archives of Internal Medicine, vol. 159, no. 14, July 26, 1999).

The investigators and other health educators believe that if carriers were better informed about their risks they might be more likely to disclose them. Pretest education and counseling were seen as key to increasing carriers' understanding of the significance of findings and their family planning options. For example, when both parents are carriers, the risk of their child having CF is one in four, and the risk of their child being a carrier is one in two. When both parents are carriers, they may choose to have prenatal diagnosis using CVS or amniocentesis to find out whether their unborn child will have the disease. Alternatively, they may choose to use assisted reproductive technology such as in vitro fertilization (the egg and sperm are united outside of the body), because it offers the option of preimplantation diagnosis. Preimplantation genetic diagnosis enables parents undergoing in vitro fertilization to screen an embryo for CF genetic mutations before it is implanted in the uterus.

Huntington's Disease

Named for the American physician George Sumner Huntington (1850–1916), Huntington's disease (HD), or Huntington's chorea, is an inherited, progressive brain disorder. It causes the degeneration of cells in the basal ganglia, a pair of nerve clusters deep in the brain that affect both the body and the mind. HD is caused by a single dominant gene that affects men and women of all races and ethnic groups.

The gene mutation that produces HD was mapped to chromosome 4 in 1983 and cloned in 1993. The mutation is in the DNA that codes for the protein huntingtin. The number of repeated triplets of nucleotides—cytosine (C), thymine (T), and guanine (G), known as CTG (nucleotides are nitrogen-containing molecules that link together to form strands of DNA and RNA)—is inversely related to the age when the individual first experiences symptoms: the more repeated triplets, the younger the age of onset of the disease. Like myotonic dystrophy, in which the symptoms of the disease often increase in severity from one generation to the next, the unstable triplet repeat sequence can lengthen from one generation to the next, with a resultant decrease in the age when symptoms first appear.

HD does not usually strike until mid-adulthood, between ages thirty and fifty, although there is a juvenile form that can affect children and adolescents. Early symptoms, such as forgetfulness, a lack of muscle coordination, or a loss of balance, are often ignored, delaying the diagnosis. The disease gradually takes its toll over a ten- to twenty-five-year period.

Within a few years, characteristic involuntary movement (chorea) of the body, limbs, and facial muscles appears. As HD progresses, speech becomes slurred and swallowing becomes difficult. The patients' cognitive abilities decline and there are distinct personality changes—depression and withdrawal, sometimes countered with euphoria. Eventually, nearly all patients must be institutionalized, and they usually die as a result of choking or infections.


HD, once considered rare, is now recognized as one of the more common hereditary diseases. According to the National Institute of Neurological Disorders and Stroke (, HD is known to affect about thirty thousand Americans; another one hundred and fifty thousand are at a 50% risk of inheriting it from an affected parent. Estimates of its prevalence are about one in ten thousand persons.


In 1983 researchers identified a DNA marker that made it possible to offer a test to determine, before symptoms appear, whether an individual has inherited the HD gene. In some cases it is even possible to make a prenatal diagnosis on the unborn child. Many people, however, prefer not to know whether or not they carry the defective gene.

For those who have had testing for HD, a positive result rarely brings shock or denial, according to those who conduct pre- and posttest counseling. Most people who learn that they will eventually develop the disease are upset, but there is an acceptance of their fate. Among those whose tests come back negative, there is often a newfound freedom. They are more willing to set goals and enjoy life.


In July 2005 researchers at Johns Hopkins University School of Medicine reported the discovery of a key regulatory molecule whose overactivation by the abnormal protein produced in HD causes the characteristic symptoms of the disease. The abnormal HD protein activates the regulatory protein called p53, which in turn switches on a host of other genes. This abnormal gene activation causes the cells' mitochondria to malfunction, and kills brain cells (Akira Sawa et al., "p53 Mediates Cellular Dysfunction and Behavioral Abnormalities in Huntington's Disease," Neuron, vol. 47, July 7, 2005).

In November 2005 Professor Marina Lynch and her associates from the Institute of Neuroscience at Trinity College in Dublin reported at the 35th Annual Society for Neuroscience Meeting in Washington, D.C., that use of a neuro anti-inflammatory drug called Miraxion appeared to protect the brain from inflammation often associated with a number of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's. The investigators assert that determining exactly how Miraxion functions in the brain and establishing its neuroprotective effects is fundamental to improving understanding of its mechanism of action in neurodegenerative diseases ("Amarin Announces Significant Neuroprotective Effects of Miraxion,"

Muscular Dystrophy

Muscular dystrophy (MD) is a term that applies to a group of hereditary muscle-destroying disorders. According to the Muscular Dystrophy Association (MDA;, in 2006 some type of MD affected approximately one million Americans. Each variant of the disease is caused by defects in the genes that play important roles in the growth and development of muscles. In MD the proteins produced by the defective genes are abnormal, causing the muscles to waste away. Unable to function properly, the muscle cells die and are replaced by fat and connective tissue. The symptoms of MD may not be noticed until as much as 50% of the muscle tissue has been affected.

All of the various disorders labeled MD cause progressive weakening and wasting of muscle tissues. They vary, however, in the usual age at the onset of symptoms, rate of progression, and initial group of muscles affected. The most common childhood type, Duchenne MD, affects young boys, who show symptoms in early childhood and usually die from respiratory weakness or damage to the heart before adulthood. The gene is passed from the mother to her children. Females who inherit the defective gene generally do not manifest symptoms—they become carriers of the defective genes, and their children have a 50% chance of inheriting the disease. Other forms of MD manifest later in life and are usually not fatal.

In 1992 scientists discovered the defect in the gene that causes myotonic dystrophy, the most common adult form of MD. In people with this disorder, a segment of the gene is enlarged and unstable. This finding helps physicians more accurately diagnose myotonic dystrophy. Researchers since have identified genes linked to other types of MD, including Duchenne MD, Becker MD, limb-girdle MD, and Emery-Dreifuss MD.

In January 2005 researchers from the Mayo Clinic in Rochester, Minnesota, identified a new form of muscular dystrophy that involves mutations in a protein called ZASP, which binds to cardiac (heart) and skeletal muscles. The researchers detected ZASP mutations in eleven patients; in seven of these, they observed a dominant pattern of inheritance (Duygu Selcen and Andrew G. Engel, "Mutations in ZASP Define a Novel Form of Muscular Dystrophy in Humans," Annals of Neurology, vol. 57, February 2005).


There is no cure for MD, but patients can be made more comfortable and functional by a combination of physical therapy, exercise programs, and orthopedic devices (special shoes, braces, or powered wheelchairs) that help them to maintain mobility and independence as long as possible.

Genetic research offers hope of finding effective treatments, and even cures, for these diseases. Gene therapy experiments specifically aimed toward a cure or a treatment for one or more of these types of MD are under way. Research teams have identified the crucial proteins produced by these genes, such as dystrophin, beta sarcoglyan, gamma sarcoglyan, and adhalin.

Because defective or absent proteins cause MD, researchers hope that experimental treatments to transplant normal muscle cells into wasting muscles will replace the diseased cells. Muscle cells, unlike other cells in the body, fuse together to become giant cells. Scientists hope that if cells with healthy genes can be introduced into the muscles and accepted by the body's immune system, the muscle cells will then begin to produce the missing proteins.

New delivery methods called vectors also are being tested, which involves implanting a healthy gene into a virus that has been stripped of all of its harmful properties and then injecting the modified virus into a patient. Researchers hope this will reduce the amount of rejection by the patient's immune system, allowing the healthy gene to restore the missing muscle protein.

At a November 2005 conference sponsored by the MDA and the University of Arizona College of Medicine, investigators described how the study of the genes involved in MD and development of new methods for pinpointing each patient's precise mutation guided development of molecular strategies for the treatment of Duchenne MD. PTC Therapeutics, a biotechnology company in New Jersey, with support from the MDA, has developed an experimental drug called PTC124 that has proven safe in preliminary human trials ("MDA Gathers Scientists, Physicians for Updates on Research Progress," MDA Research News, December 8, 2005,

Sickle Cell Disease

Sickle cell disease (SCD) is a group of hereditary diseases, including sickle cell anemia and sickle B-thalassemia, in which the red blood cells contain an abnormal hemoglobin, termed hemoglobin S. Hemoglobin S is responsible for the premature destruction of red blood cells, or hemolysis. In addition, it causes the red cells to become deformed, actually taking on a sickle shape, particularly in parts of the body where the amount of oxygen is relatively low. These abnormally shaped cells cannot travel smoothly through the smaller blood vessels and capillaries. They tend to clog the vessels and prevent blood from reaching vital tissues. This blockage produces anoxia (lack of oxygen), which in turn causes more sick-ling and more damage.


People with sickle cell anemia have the symptoms of anemia, including fatigue, weakness, fainting, and palpitations or an increased awareness of their heartbeat. These palpitations result from the heart's attempts to compensate for the anemia by pumping blood faster than normal.

In addition, patients experience occasional sickle cell crises—attacks of pain in the bones and stomach. Blood clots also may develop in the lungs, kidneys, brain, and other organs. A severe crisis or several acute crises can damage the organs of the body by impeding the flow of blood. This damage can lead to death from heart failure, kidney failure, or stroke. The frequency of these crises varies from patient to patient. A sickle cell crisis, however, occurs more often during infections and after an accident or an injury.

In 2004 the New England Journal of Medicine (Mark T. Gladwin et al, "Pulmonary Hypertension as a Risk Factor for Death in Patients with Sickle Cell Disease," vol. 350, no. 9, February 26, 2004) reported that researchers from the NIH and the Howard University Center for Sickle Cell Disease found that one-third of patients with SCD who had been screened with a noninvasive ultrasound method were found to have previously undetected moderate to severe pulmonary hypertension. This confirms earlier suggestions that pulmonary hypertension occurs in about 20%-40% of patients with SCD, which poses major health risks, including death. The researchers suggested that these findings were "so striking" that all patients with sickle cell should be regularly screened for hypertension and subsequently treated.


Both the sickle cell trait and the disease exist almost exclusively in people of African, American Indian, and Hispanic descent and in people from parts of Italy, Greece, the Middle East, and India. When one parent has the sickle cell gene, a couple's offspring will carry the trait but only if both the mother and the father have the trait can they produce a child with sickle cell anemia. According to the National Heart, Lung, and Blood Institute (NHLBI is an institute of the NIH;, SCD occurs in about seventy-two thousand Americans, most of whom are of African descent. The disease occurs in approximately one in five hundred African-American births and one in every one thousand to fourteen hundred Hispanic American births. Approximately two million Americans—including one in every twelve African-Americans—carry the sickle cell trait. Americans of African descent are advised to seek genetic counseling and testing for the trait before starting a family.

Testing is done by taking a sample of the amniotic fluid or tissue taken from the placenta as early as the first trimester of pregnancy. A genetic counselor evaluates the results and will be able to tell the parents what the chances are that their child will have the sickle cell trait or sickle cell anemia. Table 4.4 shows the average prevalence of SCD per one hundred thousand live births in the United States among different racial and ethnic groups.


In 1993 a federal panel of researchers, clinicians, and policy makers called for SCD screening of all newborns, because early diagnosis and treatment significantly improves future health. Because of intermarriage, it is becoming more difficult to be certain of a person's racial or ethnic background based on physical appearance, surname, or self-reporting. Many SCD sufferers could possibly be missed by exclusively screening a target population such as African-Americans.

Prevalence of sickle cell diseases by race or ethnic group, 1990 and unspecified years
Race or ethnic groupAverage prevalence per 100,000 live births
Note: Sickle cell diseases include Hb SS, sickle cell-hemoglobin C disease, and sickle beta-thalassemia syndromes.
source: Richard S. Olney, "Table 2. Prevalence of Sickle Cell Disease (Hb SS, Sickle Cell-Hemoglobin C Disease and Sickle Beta-Thalassemia Syndromes) by Racial or Ethnic Group, per 100,000 Live Births, United States, 1990 and Unspecified Years," in "Newborn Screening for Sickle Cell Disease: Public Health Impact and Evaluation" Genetics and Public Health in the 21st Century, Centers for Disease Control and Prevention, (accessed December 29, 2005)
White  1.72
Hispanic, total  5.28
Hispanic, eastern states 89.8
Hispanic, western states  3.14
Asian  7.61
Native American 36.2

By 1993, thirty-four states and jurisdictions had already instituted the universal screening of infants recommended by an earlier study group of the NIH in 1988. Another ten states had targeted screening aimed at groups traditionally considered at higher risk, and eight states and jurisdictions had no sickle cell screening program. The cost of universal screening has not been studied, but many researchers and policymakers feel that the investment would pay great dividends. A machine to run sickle cell tests could cost between $5,000 and $30,000; material to conduct a single test costs $1 to $3. The American Academy of Pediatrics, the American Nurses Association, the National Medical Association (an organization of African-American physicians), and the Sickle Cell Disease Association of America endorsed the new guidelines for universal screening.

Early diagnosis (soon after birth) could save the lives of children born with SCD. Studies have found wide differences in the mortality rates of children with SCD. To improve survival rates for children with SCD living in high mortality areas, public health advocates recommend further study of the accessibility and quality of available screening and medical care and the duplication of successful treatment programs. In addition, they emphasize the importance of educating parents about the disease and its treatments ("Mortality among Children with Sickle Cell Disease Identified by Newborn Screening during 1990–1994—California, Illinois, and New York," Mortality and Morbidity Weekly Report, vol. 46, no. 9, March 13, 1998; "Geographic Differences in Mortality of Young Children with Sickle Cell Disease in the United States," Public Health Reports, vol. 112, no. 1, January/February 1997).


There is no universal cure for SCD, but the symptoms can be treated. Crises accompanied by extreme pain are the most common problems and usually can be treated with pain relievers. Maintaining healthy eating and lifestyle and prompt treatment for any type of infection or injury are important. Special precautions are often necessary before any type of surgery; for major surgery some patients receive transfusions to boost their levels of hemoglobin (the oxygen-bearing, iron-containing protein in red blood cells). In early 1995 a medication that prevented the cells from clogging vessels and cutting off oxygen was approved. Blood transfusions also may be used to treat or prevent associated problems, such as anemia, spleen enlargement, and recurring stroke.

At the 1993 National Institutes of Health Consensus Conference, a federal panel of experts on SCD recommended that all infants diagnosed with the disease receive daily doses of penicillin to prevent infections. Parents are urged to make sure that these children receive the scheduled childhood immunizations and are vaccinated against influenza, pneumonia, and hepatitis B by age two years. In the mid-1980s, 20% of children with SCD died before their first birthday; by 1993, primarily because of preventive antibiotics, that proportion had dropped to less than 3%. Although there are neither uniform SCD reporting nor national reports of incidence or prevalence, public health professionals believe that antibiotic prophylaxis (preventive treatment) has further reduced SCD mortality (Sickle Cell Guideline Panel, Sickle Cell Disease: Screening, Diagnosis, Management and Counseling in Newborns and Infants, Clinical Practice Guideline No. 6, Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services, April 1993).


Today, many adults with SCD take hydroxyurea, an anticancer drug that causes the body to produce red blood cells that resist sickling. In 1995 a multicenter study showed that among adults with three or more painful crises per year, hydroxyurea lowered the median number of crises requiring hospitalization by 58%. In 2003 an extension of that study showed that patients on hydroxyurea not only have fewer crises but also have a significant survival advantage when compared with SCD patients who do not take the medication. Subjects treated with it overall showed 40% lower mortality than others (Martin H. Steinberg et al., "Effect of Hydroxyurea on Mortality and Morbidity in Adult Sickle Cell Anemia: Risks and Benefits Up to 9 Years of Treatment," Journal of the American Medical Association, April 2, 2003).

A 1996 international study found that bone marrow transplants were successful in curing SCD in sixteen of twenty-two patients—72.7% of the patients in the five-year study. Bone marrow is where new blood cells are produced. All of the participants in the study were under age fourteen years, had advanced symptoms, and had siblings who were compatible bone marrow donors. Four of the patients (18%) rejected the donor marrow, and their SCD symptoms returned. Two of the patients (9%) died ("Bone Marrow Transplantation for Sickle Cell Disease: A Multicenter Collaborative Investigation," New England Journal of Medicine, August 8, 1996).

Because of the high risks of bone marrow transplants and the difficulties of matching donors, transplants are not appropriate for every patient. Further studies are needed to test the procedure with older patients and to reduce the proportion of tissue rejects. Blood harvested from umbilical cords and placentas has been found to be less likely to trigger rejection or graft-versus-host disease, in which the transplanted cells attack the cells of the bone marrow recipient, causing organ damage.

Tay-Sachs Disease

Tay-Sachs disease (sometimes referred to as TSD) is a fatal genetic disorder in children that causes the progressive destruction of the central nervous system. It is caused by the absence of an important enzyme called hexosaminidase A (hex-A). Without hex-A, a fatty substance called GM2 ganglioside builds up abnormally in the cells, particularly the brain's nerve cells. Eventually, these cells degenerate and die. This destructive process begins early in the development of a fetus, but the disease usually is not diagnosed until the baby is several months old. By the time a child with TSD is four or five years old, the nervous system is so badly damaged that the child dies.


A baby with TSD seems normal at birth and usually develops normally for about the first six months of life, but then development slows. The child begins to regress and loses skills one by one—the ability to crawl, to sit, to reach out, and to turn over. The victim gradually becomes blind, deaf, and unable to swallow. The muscles begin to atrophy, and paralysis sets in. Mental retardation occurs, and the child is unable to relate to the outside world. Death usually occurs between ages three and five. There is no cure or treatment for this disease.


TSD is transmitted from parent to child the same way eye or hair color is inherited. Both the mother and the father must be carriers of the TSD gene to give birth to a child with the disease.

People who carry the gene for TSD are entirely unaffected and usually are unaware that they have the potential to pass this disease to their offspring. When only one parent is a carrier, the couple will not have a child with TSD. When both parents carry the recessive TSD gene, they have a one in four chance in every pregnancy of having a child with the disease. They also have a 50% chance of bearing a child who is a carrier. Prenatal diagnosis early in pregnancy can predict if the unborn child has TSD. If the fetus has the disease, the couple may choose to terminate the pregnancy.


Some genetic diseases, such as TSD, occur most frequently in a specific population. Individuals of Eastern European (Ashkenazi) Jewish descent have the highest risk of being carriers of TSD. According to the National Tay-Sachs and Allied Diseases Association, approximately one in every twenty-seven Jews in the United States is a carrier of the TSD gene, and 85% of the children who are victims of this disease are Jewish. Italians also have a higher than average risk of being carriers. In the general population, the carrier rate is one in 250.

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