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Mucolipidosis (ML) is a group of rare, inherited disorders that are characterized by the accumulation of complex fats, called mucolipids, in the cells of the body. The symptoms range from skeletal abnormalities and vision problems to physical and mental retardation.


Types of mucolipidosis

There are three major types of mucolipidosis. Mucolipidosis II (ML II, ML2) or ML disorder type II, is known as I-cell disease (ICD). Sometimes it is called Leroy disease, after Jules Leroy who described the disorder in 1969. ML II is also known as N-acetylglucosamine-1-phosphotransferase (GNPTA) deficiency. GNPTA is the enzyme that is defective in ML II.

Mucolipidosis III (ML III, ML3), or ML disorder III, is a milder form of ML II. In ML III, the enzyme GNPTA has reduced activity; whereas it has no activity in ML II. ML III was first described in 1966. It is often called pseudo-Hurler polydystrophy because its symptoms resemble a mild form of the mucopolysaccharide disorder known as Hurler syndrome. It is a polydystrophy because several systems of the body are affected.

In the past, ML II and ML III were classified as mucopolysaccharidoses (MPS II and MPS III, respectively). MPS is a condition in which complex sugars called mucopolysaccharides accumulate in the cells of the body. Although this may occur in ML, excess amounts of mucopolysaccharides are not excreted in the urine, as they are in MPS.

Mucolipidosis IV (ML IV, ML4) was first described in 1974. It also is called ML disorder IV, Berman syndrome, or sialolipidosis.

Neuraminidase deficiency originally was classified as mucolipidosis I (ML I). However, neuraminidase deficiency does not involve the accumulation of mucolipids.


Lipids are large, complex biomolecules that are very important components of cell membranes. They also are used to store energy and are present in mucus secretions.

Lipids are continually broken down and replaced. This breakdown of lipids occurs in a membrane-bound compartment or organelle within cells, called the lysosome. The lysosome contains many enzymes that break down the lipids. These enzymes are produced outside of the lysosome and have to be transported into the organelle. The enzyme GNPTA attaches a signal to these enzymes that directs them to the lysosome.

Lysosomal storage diseases

MLs are classified as lysosomal storage diseases because the lysosomes accumulate lipids that cannot be broken down. Eventually, the lysosomes become so filled with lipids that the cells form structures called inclusion bodies to contain the lipids. Inclusion bodies give the cells a characteristic appearance. The name "I-cell disease" refers to these inclusion bodies.

Individuals with ML II or ML III have little or no GNPTA enzyme activity. Thus, the lysosomal enzymes cannot reach the lysosome to help break down lipids. ML II and ML III are caused by mutations, or changes, in one of the genes that encodes a part of GNPTA. A disorder called mucolipidosis III, variant form, or complementation group C, is caused by a mutation in a gene that encodes a different part of GNPTA. However, the symptoms of this form of ML III are very similar to those of the more common type of ML III.

ML IV is caused by a mutation in the gene encoding a protein called mucolipin-1. In ML IV, membrane lipids and mucopolysaccharides accumulate in the lysosomes of cells throughout the body. Apparently, in the absence of mucolipin-1, these substances are transported to the lysosome rather than recycled to the cell membrane.

Genetic profile

All of the MLs are inherited as autosomal recessive traits. They are autosomal because the genes that are responsible for these disorders are located on autosomal chromosomes, rather than on the X or Y sex chromosomes. The traits are recessive because they are only expressed in individuals who have inherited two copies of the gene that causes the disorder, one copy from each parent.

Individuals with only one copy of a gene that causes ML are called carriers. They usually do not have symptoms of ML. The offspring of two carriers of an ML gene have a 25% chance of inheriting both genes and developing ML.


MLs are very rare disorders that often have been misdiagnosed. Thus, the frequency of ML is not clear. However, since MLs are recessive disorders that only develop when both parents are carriers of one of the ML genes, the condition most often occurs in the offspring of closely-related individuals, such as first cousins. These disorders are much more prevalent in small, isolated populations. For example, among French-Canadians in one region of Quebec province, it is estimated that one out of every 39 people carries a gene for ML II and one out of 6,184 infants has the disorder. In contrast, over a 10-year-period, only 35 infants with ML II or ML III were born in Great Britain.

Although ML IV can occur in any nationality or ethnic group, more than 80% of all known cases are Jews of Eastern European descent (Ashkenazim). It is estimated that one out of 50 individuals of Ashkenazi descent is a carrier of ML IV. Worldwide, there are about 100 known cases of the disorder. However, it is thought that there are many more undiagnosed or misdiagnosed cases.

Signs and symptoms

The symptoms and the age of onset of ML II vary greatly, even within families. Some signs of ML II can be congenital, or present at birth. These may include:

  • Multiple abnormalities in bone formation, particularly in the hip
  • Limited mobility of the joints
  • Multiple abnormalities of the skull and face
  • A fold of skin extending from the inner corner of the eyelid, called an epicanthal fold

ML II and ML III are progressive conditions. Infants may show few symptoms of the disorder until lipids begin to accumulate and damage cells. Additional symptoms of ML II may include:

  • Dwarfism
  • Delayed mental and physical development
  • Hearing loss
  • Heart disease in the aortic valve
  • Swollen liver and spleen

The symptoms of ML III are similar to those of ML II, but usually less severe. Additional signs of ML III may include:

  • Acne
  • Clouding of the cornea, the clear portion of the eye through which light passes
  • Enlarged tongue

ML IV is characterized by mental and physical retardation and eye disorders. Many individuals with ML IV do not develop beyond the skill level of a one-year-old. However, some individuals with ML IV have very mild symptoms.

Infants with ML IV appear normal at birth. However signs of the disorder usually become apparent during the first year. Often, clouding or opacity of the cornea is the first symptom and vision problems may develop before the age of one. The physical and mental retardation may be mild at first, but often becomes severe as the disorder slowly progresses. Most individuals with ML IV never walk. Other signs of ML IV may include:

  • Delayed growth
  • Poor muscle tone
  • Crossed eyes
  • Puffy eyelids
  • Aversion to light
  • Degeneration of the retina, eventually leading to blindness


ML II and ML III may be diagnosed by high levels of lysosomal enzymes, called hydrolases, in the blood. The absence of mucopolysaccharides in the urine indicates that the disorder is not a mucopolysaccharidosis. The microscopic examination of various cells reveals inclusion bodies. X rays are used to detect skeletal abnormalities.

The initial diagnosis of ML IV usually results from a biopsy. A small piece from the skin or from the membrane underneath the eyelid is removed and examined under a microscope for the accumulation of lipids and mucopolysaccharides in storage bodies.

Treatment and management

There is no cure for ML. Management of symptoms, close medical monitoring, and supportive care are the primary treatments.

Surgery can remove the thin layer of cells that causes the corneal cloudiness that is characteristic of ML IV. However, the layer of cells will grow back. Physical, occupational, and speech therapy can improve the functioning of children with ML IV.


The life expectancy for individuals with ML is not known.



Bargal, R., et al. "Identification of the Gene Causing Mucolipidosis Type IV." Nature Genetics 26 (2000): 118-121.

Olkkonen, V. M., and E. Ikonen. "Genetic Defects of Intracellular-Membrane Transport." New England Journal of Medicine 343 (2000): 1095-1104.


Canadian Society for Mucopolysaccharide and Related Diseases. PO Box 64714, Unionville, ONT L3R OM9. Canada (905) 479-8701 or (800) 667-1846. <>.

Mucolipidosis IV Foundation. 719 East 17th St., Brooklyn, NY 11230. (718) 434-5067. <>.

National Foundation for Jewish Genetic Diseases, Inc. 250 Park Ave., Suite 1000, New York, NY 10017. (212) 371-1030. <>.

National MPS Society. 102 Aspen Dr., Downingtown, PA 19335. (610) 942-0100. Fax: (610) 942-7188. [email protected]. <>.


"Medical Information." Mucolipidosis IV Foundation. (April 24, 2001). <>.

"Mucolipidosis IV." National Foundation for Jewish Genetic Diseases, Inc. (April 24, 2001). <>.

"Mucolipidosis IV." University of Pittsburgh Department of Human Genetics. [June 1, 2000]. (April 24, 2001). <>.

Margaret Alic, PhD