Galactosemia is an inherited disease in which the transformation of galactose to glucose is blocked, allowing galactose to increase to toxic levels in the body. If galactosemia is untreated, high levels of galactose cause vomiting, diarrhea, lethargy, low blood sugar, brain damage, jaundice, liver enlargement, cataracts, susceptibility to infection, and death.
Galactosemia is a rare but potentially life-threatening disease that results from the inability to metabolize galactose. Serious consequences from galactosemia can be prevented by screening newborns at birth with a simple blood test.
Galactosemia is an inborn error of metabolism. "Metabolism" refers to all chemical reactions that take place in living organisms. A metabolic pathway is a series of reactions where the product of each step in the series is the starting material for the next step. Enzymes are the chemicals that help the reactions occur. Their ability to function depends on their structure, and their structure is determined by the deoxyribonucleic acid (DNA) sequence of the genes that encode them. Inborn errors of metabolism are caused by mutations in these genes which do not allow the enzymes to function properly.
Sugars are sometimes called "the energy molecules," and galactose and glucose are both sugars. For galactose to be utilized for energy, it must be transformed into something that can enter the metabolic pathway that converts glucose into energy (plus water and carbon dioxide). This is important for infants because they typically get most of their nutrient energy from milk, which contains a high level of galactose. Each molecule of lactose, the major sugar constituent of milk, is made up of a molecule of galactose and a molecule of glucose, and so galactose makes up 20% of the energy source of a typical infant's diet.
Three enzymes are required to convert galactose into glucose-1-phosphate (a phosphorylated glucose that can enter the metabolic pathway that turns glucose into energy). Each of these three enzymes is encoded by a separate gene. If any of these enzymes fail to function, galactose build-up and galactosemia result. Thus, there are three types of galactosemia with a different gene responsible for each.
Every cell in a person's body has two copies of each gene. Each of the forms of galactosemia is inherited as a recessive trait, which means that galactosemia is only present in individuals with two mutated copies of one of the three genes. This also means that carriers, with only one copy of a gene mutation, will not be aware that they are carrying a mutation (unless they have had a genetic test), as it is masked by the normal gene they also carry and they have no symptoms of the disease. For each step in the conversion of galactose to glucose, if only one of the two copies of the gene controlling that step is normal (i.e. for carriers), enough functional enzyme is made so that the pathway is not blocked at that step. If a person has galactosemia, both copies of the gene coding for one of the enzymes required to convert glucose to galactose are defective and the pathway becomes blocked. If two carriers of the same defective gene have children, the chance of any of their children getting galactosemia (the chance of a child getting two copies of the defective gene) is 25% (one in four) for each pregnancy.
Classic galactosemia occurs in the United States about one in every 50,000-70,000 live births.
Causes and symptoms
Galactosemia I (also called classic galactosemia), the first form to be discovered, is caused by defects in both copies of the gene that codes for an enzyme called galactose-1-phosphate uridyl transferase (GALT). There are 30 known different mutations in this gene that cause GALT to malfunction.
Newborns with galactosemia I appear normal at birth, but begin to develop symptoms after they are given milk for the first time. Symptoms include vomiting, diarrhea, lethargy (sluggishness or fatigue ), low blood glucose, jaundice (a yellowing of the skin and eyes), enlarged liver, protein and amino acids in the urine, and susceptibility to infection, especially from gram negative bacteria. Cataracts (a grayish white film on the eye lens) can appear within a few days after birth. People with galactosemia frequently have symptoms as they grow older even though they have been given a galactose-free diet. These symptoms include speech disorders, cataracts, ovarian atrophy, and infertility in females, learning disabilities, and behavioral problems.
Galactosemia II is caused by defects in both copies of the gene that codes for an enzyme called galactokinase (GALK). The frequency of occurrence of galactosemia II is about one in 100,000-155,000 births.
Galactosemia II is less harmful than galactosemia I. Babies born with galactosemia II will develop cataracts at an early age unless they are given a galactose-free diet. They do not generally suffer from liver damage or neurologic disturbances.
Galactosemia III is caused by defects in the gene that codes for an enzyme called uridyl diphosphogalactose-4-epimerase (GALE). This form of galactosemia is very rare.
There are two forms of galactosemia III, a severe form, which is exceedingly rare, and a benign form. The benign form has no symptoms and requires no special diet. However, newborns with galactosemia III, including the benign form, have high levels of galactose-1-phosphate that show up on the initial screenings for elevated galactose and galactose-1-phosphate. This situation illustrates one aspect of the importance of follow-up enzyme function tests. Tests showing normal levels of GALT and GALK allow people affected by the benign form of galactosemia III to enjoy a normal diet.
The severe form has symptoms similar to those of galactosemia I, but with more severe neurological problems, including seizures. Only two cases of this rare form had been reported as of 1997.
The newborn screening test for classic galactosemia is quick and straightforward; all but three states require testing on all newborns. Blood from a baby who is two to three days old is usually first screened for high levels of galactose and galactose-1-phosphate. If either of these compounds is elevated, further tests are performed to find out which enzymes (GALT, GALK, or GALE) are present or missing. DNA testing may also be performed to confirm the diagnosis.
If there is a strong suspicion that a baby has galactosemia, galactose is removed from the diet right away. In this case, an initial screen for galactose or galactose-1-phosphate will be meaningless. In the absence of galactose in the diet, this test will be negative whether the baby has galactosemia or not. In this case, tests to measure enzyme levels must be given to find out if the suspected baby is indeed galactosemic.
In addition, galactosemic babies who are refusing milk or vomiting will not have elevated levels of galactose or galactose phosphate, and their condition will not be detected by the initial screen. Any baby with symptoms of galactosemia (for example, vomiting) should be given enzyme tests.
Galactosemia I and II are treated by removing galactose from the diet. Since galactose is a breakdown product of lactose, the primary sugar constituent of milk, this means all milk and foods containing milk products must be totally eliminated. Other foods like legumes, organ meats, and processed meats also contain considerable galactose and must be avoided. Pills that use lactose as a filler must also be avoided. Soybased and casein hydrolysate-based formulas are recommended for infants with galactosemia.
Treatment of the severe form of galactosemia III with a galactose-restricted diet has been tried, but this disorder is so rare that the long-term effects of this treatment are unknown.
Early detection in the newborn period is the key to controlling symptoms. Long-term effects in untreated babies include severe mental retardation, cirrhosis of the liver, and death. About 75% of the untreated babies die within the first two weeks of life. On the other hand, with treatment, a significant proportion of people with galactosemia I can lead nearly normal lives, although speech defects, learning disabilities, and behavioral problems are common. A 2004 study revealed that children and adolescents with classic galactosemia often have lower quality of life than peers without the disease, exhibiting problems with cognition (thinking and intellectual skills) and social function. In addition, cataracts due to galactosemia II can be completely prevented by a galactose-free diet.
Casein hydrolysate— A preparation made from the milk protein casein, which is hydrolyzed to break it down into its constituent amino acids. Amino acids are the building blocks of proteins.
Catalyst— A substance that changes the rate of a chemical reaction, but is not physically changed by the process.
Enzyme— A protein that catalyzes a biochemical reaction or change without changing its own structure or function.
Galactose— One of the two simple sugars, together with glucose, that makes up the protein, lactose, found in milk. Galactose can be toxic in high levels.
Glucose— One of the two simple sugars, together with galactose, that makes up the protein, lactose, found in milk. Glucose is the form of sugar that is usable by the body to generate energy.
Lactose— A sugar made up of of glucose and galactose. It is the primary sugar in milk.
Metabolic pathway— A sequence of chemical reactions that lead from some precursor to a product, where the product of each step in the series is the starting material for the next step.
Metabolism— The total combination of all of the chemical processes that occur within cells and tissues of a living body.
Recessive trait— An inherited trait or characteristic that is outwardly obvious only when two copies of the gene for that trait are present.
Since galactosemia is a recessive genetic disease, the disease is usually detected on a newborn screening test, since most people are unaware that they are carriers of a gene mutation causing the disease. For couples with a previous child with galactosemia, prenatal diagnosis is available to determine whether a pregnancy is similarly affected. Families in which a child has been diagnosed with galactosemia can have DNA testing which can enable other more distant relatives to determine their carrier status. Prospective parents can then use that information to conduct family planning or to prepare for a child with special circumstances. Children born with galactosemia should be put on a special diet right away, to reduce the symptoms and complications of the disease.
Bosch, Annet M., et al. "Living With Classical Galactosmeia: Health-related Quality of Life Consequences." Pediatrics May 2004: 1385-1387.
Association for Neuro-Metabolic Disorders. 5223 Brookfield Lane, Sylvania, OH 43560. (419) 885-1497.
Metabolic Information Network. PO Box 670847, Dallas, TX 75367-0847. (214) 696-2188 or (800) 945-2188.
Parents of Galactosemic Children, Inc. 2148 Bryton Dr., Powell OH 43065. 〈http://www.galactosemia.org/index.htm〉.
"GeneCards: Human Genes, Proteins and Diseases." 〈http://bioinfo.weizmann.ac.il/cards/〉.
"Vermont Newborn Screening Program: Galactosemia." 〈http://www.vtmednet.org/∼m145037/vhgi_mem/nbsman/galacto.htm〉.
"Galactosemia." Gale Encyclopedia of Medicine, 3rd ed.. . Encyclopedia.com. (August 23, 2017). http://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/galactosemia-0
"Galactosemia." Gale Encyclopedia of Medicine, 3rd ed.. . Retrieved August 23, 2017 from Encyclopedia.com: http://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/galactosemia-0
Galactosemia is an inherited disease in which the body is unable to metabolize the simple sugar galactose, which is found primarily in dairy products but is also produced by the body. If left unaddressed, galactose can increase to toxic levels in the body and may lead to damage of the liver, central nervous system, and various other body systems.
Galactosemia is a rare but potentially life-threatening disease resulting from the body's inability to metabolize galactose. Galactose makes up half of lactose, the sugar that is found in milk. Persons with galactosemia either have very low levels of or are entirely lack the enzyme that assists the body in breaking down galactose. This enzyme is called galactose-1-phosphate uridyl transferase (GALT). The GALT enzyme enables the body to break down galactose into glucose for energy. The severity of the disease may vary from person to person, because some individuals with galactosemia have higher levels of this enzyme than do others.
The two main types of galactosemia are called classic and Duarte variant. Individuals with the classic type of galactosemia lack the enzyme activity necessary to metabolize galactose. Individuals with the Duarte variant have approximately 5–20 percent of the enzyme activity necessary to metabolize this sugar and often do not have signs or symptoms of galactosemia.
Galactosemia is an hereditary disease. In order to understand this disorder, it is necessary to have a very basic knowledge of genetics. Genes, the basic components of hereditary material, contain the "blueprint" that directs the development and functioning of every cell and tissue in the human body. Genes are situated on larger structures called chromosomes that contain several thousand genes each. Genes and chromosomes exist in pairs. Every cell in the body has 23 pairs of chromosomes containing two copies of every gene. Human beings receive one copy of every gene from their mother, and another copy from their father. Most of the time, genes function normally. However, in some cases, a change or mutation in a gene can cause it to not function. These mutations can cause inherited or genetic disorders.
In galactosemia, the gene mutation which occurs is inherited in what is known as an autosomal recessive pattern. This means that a non-working copy of the gene must be inherited from both parents for a child to be affected with the disease. The parents of children are called "carriers" of the disorder, because though they themselves do not have galactosemia, they may have children who do.
Unfortunately, as of 2004, parents had no way of knowing if they carry the mutated gene that causes galactosemia until they have a child diagnosed with the disease. The chance that two parents each of whom has the defective gene will produce a child with a recessive disorder is one in four or 25 percent with each pregnancy. The chances that their child will be a carrier, like themselves, is one in two, or 50 percent, with each pregnancy.
Galactosemia is an inherited disorder that occurs in approximately one out of 30,000 live births. The incidence for the Duarte variant type of galactosemia is estimated to be one in 16,000 live births. Although galactosemia occurs in all ethnic groups worldwide, some mutations cause a less severe type of disease and are more commonly seen in specific ethnic groups, such as African-Americans. In Japan, classic galactosemia is not diagnosed as frequently as it is in Caucasian populations in the United States.
Causes and symptoms
Galactosemia is an inherited disorder. People with the disease are unable to fully break down galactose. If an infant with galactosemia is given milk, byproducts of galactose will build up in the baby's body, causing damage to the liver, kidneys, brain, and eyes. Characteristically, a newborn with galactosemia who is fed milk products will have jaundice , vomiting , lethargy, irritability, and convulsions. Continued feeding of milk products to the infant will lead to cirrhosis, cataracts, kidney failure, and mental retardation .
When to call the doctor
Parents should notify their doctor if their child displays any of the symptoms of galactosemia. Couples should consult their physician if there is a family history of galactosemia, and they are considering having a child.
As of late 2004, all 50 states had mandatory screening of newborns for galactosemia. If parents receive a call from a healthcare provider saying the screening test indicates possible galactosemia, they should promptly stop milk products and have a blood test done for galactosemia through their doctor. The physician may also perform enzyme studies on or look for the presence of "reducing substances" in the child's urine, look for ketones in the urine, and measure enzyme activity in the red blood cells.
Galactosemia is treated by removing foods that contain galactose from the diet. Foods containing lactose and, therefore, galactose should be avoided. Because milk and milk products are the most common food source of galactose, persons with galactosemia should avoid ingesting these foods. It is recommended that persons with galactosemia avoid eating foods with galactose throughout their entire lives.
The goal of dietary treatment is to minimize galactose intake. It is impossible to have a galactose-free diet. However, all persons with galactosemia should limit galactose intake as much as possible. The galactose-1-phosphate levels of the individual will establish the level of dietary restriction necessary. Infants can be fed soy, meat-based, or other lactose-free formulas. Abstinence from milk and milk products must continue throughout life. Parents need to find some of the many listings available that identify the galactose content in foods. Since the primary source of calcium is usually milk or milk-based foods, calcium must be supplemented. Parents of a child with galactosemia should note that lactose is often used as filler in medicines. This very frequently is not listed on the package. Parents should always check with the pharmacist before administering any new medications.
Approximately 75 percent of the babies with galactosemia who are not diagnosed and treated die within the first two weeks of life. By contrast, if an early diagnosis is made and if milk products are strictly avoided, most children lead a relatively normal life. With appropriate treatment, liver and kidney problems do not develop, and early mental development progresses in a normal manner. However, even with proper treatment, children with galactosemia often have a lower intelligence quotient (IQ) than their siblings, and they frequently have speech problems. Girls often have ovaries that do not function, and only a few are able to conceive naturally. Boys, however, have normal testicular function.
Galactose —One of the two simple sugars (glucose is the other one) that makes up the protein, lactose, found in milk. Galactose can be toxic in high levels.
Recessive trait —An inherited trait or characteristic that is outwardly obvious only when two copies of the gene for that trait are present.
Since galactosemia is a recessive genetic disease, it is usually first detected on a newborn screening test, as most people are not aware that they are carriers of a gene mutation causing the disease. If there is a family history of galactosemia, genetic counseling is recommended for prospective parents as they make decisions regarding pregnancy and prenatal testing. Once one child in a family is diagnosed with galactosemia, it is recommended that other members of the family receive genetic counseling as well.
One of the most important things parents of a child with galactosemia can do is educate themselves thoroughly on an appropriate diet. All other caregivers or teachers involved with the child need to be notified of the child's dietary restrictions, and the potential consequences if they are not maintained.
Bosch, Annet M., et al. "Living with Classical Galactosemia: Health-Related Quality of Life Consequences." Pediatrics 113 (May 2004): 5.
Weese, S. Jean. "Galactose Content of Baby Food Meats: Considerations for Infants with Galactosemia." Journal of the American Dietetic Association (March 2003).
National Newborn Screening and Genetics Resource Center. 1912 W. Anderson Lane, Suite 210, Austin, TX 78757. Web site: <http://genes-r-us.uthscsa.edu>.
"Parents of Galactosemic Children Inc." 885 Del Sol St., Sparks, NV 89436. Web site: <www.galactosemia.org>.
"Galactosemia." MedlinePlus, January 2004. Available online at <www.nlm.nih.gov/medlineplus/ency/article/000366.htm> (accessed January 6, 2005).
"Galactosemia: An Overview." Adult Metabolic Transition Project. Available online at <http://depts.washington.edu/transmet/gal.html> (accessed January 6, 2005).
Deanna M. Swartout-Corbeil, RN
"Galactosemia." Gale Encyclopedia of Children's Health: Infancy through Adolescence. . Encyclopedia.com. (August 23, 2017). http://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/galactosemia
"Galactosemia." Gale Encyclopedia of Children's Health: Infancy through Adolescence. . Retrieved August 23, 2017 from Encyclopedia.com: http://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/galactosemia
galactosemia (gəlăk´təsē´mēə), inherited metabolic disorder caused by an enzyme deficiency and transmitted as a recessive trait; it results in the accumulation of the sugar galactose in the body. The disorder is manifested soon after birth by feeding problems and diarrhea. Galactose is accumulated principally in the liver of the newborn infant, where it may induce cirrhosis, and in the lens of the eye, where cataracts may develop. Low glucose levels cause sufficient hypoglycemia to affect the central nervous system with resulting mental retardation. These ill effects can be prevented by removing milk and all other foods containing galactose and lactose from the diet.
"galactosemia." The Columbia Encyclopedia, 6th ed.. . Encyclopedia.com. (August 23, 2017). http://www.encyclopedia.com/reference/encyclopedias-almanacs-transcripts-and-maps/galactosemia
"galactosemia." The Columbia Encyclopedia, 6th ed.. . Retrieved August 23, 2017 from Encyclopedia.com: http://www.encyclopedia.com/reference/encyclopedias-almanacs-transcripts-and-maps/galactosemia