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What are mucolipidoses?

Mucolipidoses (ML) are a group of inherited metabolic diseases that affect the body's ability to carry out the normal turnover of various materials within cells. In ML, abnormal amounts of carbohydrates and fatty materials (lipids) accumulate in cells. Because our cells are not able to handle large amounts of these substances, damage to the cells occurs, causing symptoms that range from mild learning disabilities to severe intellectual impairment and skeletal deformities.

Symptoms of ML can be congenital (present at birth) or begin in early childhood or adolescence. Early symptoms can include vision problems and developmental delays. Over time, many children with ML develop poor mental capacities, have difficulty reaching normal developmental milestones, and, in many cases, eventually die of the disease.

Types of mucolipidoses

The four types of ML are sialidosis (ML I), and types II, III, and IV.

Mucolipidosis type I (ML I), or sialidosis, results from a deficiency in one of the digestive enzymes known as sialidase. The role of sialidase is to remove a particular form of sialic acid (a sugar-like molecule) from sugar-protein complexes (referred to as glycoproteins), which allows the cell to function properly. Because the enzyme is deficient, small chains containing the sugar-like material accumulate in neurons, bone marrow, and various cells that defend the body against infection.

Symptoms of ML I are either present at birth or develop within the first year of life. In many infants with ML I, excessive swelling throughout the body is noted at birth. These infants are often born with coarse facial features, such as a flat nasal bridge, puffy eyelids, enlargement of the gums, and excessive tongue size (macroglossia). Many infants with ML I are also born with skeletal malformations such as hip dislocation. Infants often develop sudden involuntary muscle contractions (myoclonus) and have red spots in their eyes (cherry-red macules). They are often unable to coordinate voluntary movement (ataxia). Tremors, impaired vision, and seizures also occur in children with ML I.

Tests reveal abnormal enlargement of the liver and spleen and extreme abdominal swelling. Infants with ML I generally lack muscle tone (hypotonia) and have impaired intellect that is either initially or progressively severe. Many individuals suffer from failure to thrive and from recurrent respiratory infections. Most infants with ML I die before age 1.

Other diseases that result from a deficiency in the sialidase enzyme are categorized in a broader group known assialidoses. Because ML I is classified as a sialidosis, it is sometimes referred to as sialidosis type II.

Sialidosis type I, a rarer form of sialidosis, occurs in children and adolescents and is often referred to as the juvenile form of the disorder. Children usually begin to show symptoms during the second decade of life, and myoclonus (brief, involuntary twitching of muscles) and cherry-red macules in the retina are often the initial symptoms. Individuals usually develop seizures and progressive deterioration of coordinated muscular and mental activities.

Mucolipidosis types II and III (ML II and ML III) result from a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase. Just as luggage in an airport is tagged to direct it to the correct destination, enzymes are often "tagged." In ML II and ML III, the deficient enzyme is supposed to tag other enzymes (activator proteins) so that they can initiate certain metabolic processes in the cell. Because the activator proteins are not properly tagged, they escape into spaces outside the cell and therefore cannot do their usual work of breaking down substances inside the cells.

ML II is also known as inclusion-cell (I-cell) disease because waste products, thought to include carbohydrates, lipids, and proteins, accumulate into masses known as inclusion bodies. When tissues are examined under a microscope, the detection of inclusion bodies often provides a diagnosis of the disease.

ML II is a particularly severe form of ML that resembles one of the mucopolysaccharidoses called Hurler syndrome. Some physical signs, such as abnormal skeletal development, coarse facial features, and restricted joint movement, may be present at birth. Children with ML II usually have enlargement of certain organs, such as the liver or spleen, and sometimes even the heart valves. Affected children often fail to grow and develop in the first months of life. Delays in the development of their motor skills are usually more pronounced than delays in their cognitive (mental processing) skills. Children with ML II eventually develop a clouding on the cornea of their eyes and, because of their lack of growth, develop short-trunk dwarfism (underdeveloped torso). These young individuals are often plagued by recurrent respiratory tract infections, including pneumonia, otitis media (middle ear infections), and bronchitis. Children with ML II generally die before their seventh year of life, often as a result of congestive heart failure or recurrent respiratory tract infections.

In contrast, symptoms of ML III are often not noticed until the child is 3-5 years of age. One of the milder forms of the MLs, ML III (sometimes referred to as pseudo-Hurler polydystrophy) also results from a deficiency or defect of the enzymeN-acetylglucosamine-1-phosphotransferase that is characteristic of ML II. However, ML III produces less severe symptoms and progresses more slowly, probably because the deficient enzyme retains some of its activity, resulting in a smaller accumulation of carbohydrates, lipids, and proteins in the inclusion bodies.

Individuals with ML III may not be cognitively impaired or only have mild cognitive problems. These individuals usually have skeletal abnormalities, coarse facial features, short height, and corneal clouding. Some individuals with ML III survive until their 40s or 50s.

Mucolipidosis type IV (ML IV) is caused by harmful alterations of a protein in the cell that is believed to be involved in the movement of molecules such as calcium across cell membranes. Many cells throughout the body are filled with granules. Most individuals with ML IV have delay of movement development and coordination, clouding of the cornea of the eye, and severely reduced vision. Typical individuals usually have an unsteady gait and do not walk independently.

ML IV individuals have occasionally been misdiagnosed as having cerebral palsy. Speech is usually severely impaired. However, some individuals with ML IV are more mildly affected and can walk and have better speech. Rare ML IV individuals may even have only the eye abnormality with no associated brain problems. Such individuals are not cognitively impaired, just visually impaired. ML IV individuals have a dramatic reduction of secretion of acid by the stomach. This alteration results in an increase of a hormone called gastrin in the blood.

Who is more likely to get mucolipidoses?

Mucolipidoses are classified as lysosomal storage diseases because they involve increased storage of substances in the lysosomes, which are specialized sac-like components within most cells. Lysosomes play a critical role in the metabolic function of our bodies. One of their primary roles is to pick up substances such as carbohydrates and lipids and break them down into smaller molecules so that they can be used again in the metabolic process. This process is possible because lysosomes contain enzymes, which are proteins that help the body's chemistry work better and faster. Working continuously, enzymes break down carbohydrates and lipids and assist in the transfer of their byproducts throughout the rest of the cell for the production of energy or excretion.

Individuals with ML are born with a genetic defect in which their bodies either do not produce enough enzymes or, in some instances, produce ineffective forms of enzymes. Without functioning enzymes (proteins), lysosomes cannot break down carbohydrates and lipids and transport them to their destination. The molecules then accumulate in the cells of various tissues in the body, leading to damage of organs.

In individuals with ML, the molecules accumulate in nerve, liver, and muscle tissue as well as in bone marrow, and this abnormal storage causes the various symptoms associated with ML. For example, excess storage of these molecules in nerve tissues can cause developmental disabilities, accumulation in the tissues of the spleen and liver can cause poor functioning of these vital organs, and excess storage in the bone marrow can damage bones, leading to skeletal deformities.

The accumulation of carbohydrates and lipids in tissue is not the result of just one deficient enzyme. Lysosomes contain as many as 40 or 50 different enzymes, each responsible for a highly specialized function. Therefore, a deficiency in one particular enzyme or activator protein causes symptoms that may be somewhat different from the symptoms caused by the deficiency of another type of enzyme.

The MLs are similar to another group of lysosomal storage diseases known as the mucopolysaccharidoses. While both conditions produce similar symptoms and are caused by the lack of enzymes necessary to break down and transport carbohydrates and lipids, the mucopolysaccharidoses result in excess sugars, known as mucopolysaccharides (now called glycosaminoglycans), in the urine. Glycosaminoglycans are not seen in urine of individuals with ML, therefore screening of the urine can help doctors distinguish between the two groups of disorders.


The mucolipidoses are inherited in an autosomal recessive manner; that is, they occur only when a child inherits two copies of the defective gene—one from each parent. When both parents carry a defective gene, each of their children faces a one in four chance of developing one of the MLs. At the same time, each child also faces a one in two chance of inheriting only one copy of the defective gene. People who have only one defective gene are known as carriers. These individuals do not develop the disease but they can pass the defective gene on to their own children. Because the defective genes involved in certain forms of ML are known, tests can identify people who are carriers in some instances.

How are mucolipidoses diagnosed and treated?

Diagnosing ML

The diagnosis of ML is based on clinical symptoms, a complete medical history, and certain laboratory tests. ML I, II, and III can be confirmed by a blood test that measures enzyme activity in the white blood cells. Activity levels that are lower than normal indicate specific enzyme deficiencies.

Another way to confirm the diagnosis is through skin biopsy. A small sample of skin is taken from the individual and grown in a cell culture. The activity of a particular enzyme in the cultured skin cells is then measured.

ML IV is suspected when cells that are easily obtained by conjunctival swabbing (from the eyes) are found to have numerous inclusions. In addition, measurement of the level of gastrin in the blood, which is significantly increased in ML IV individuals, helps to confirm the diagnosis.

Scientists have identified the genes responsible for all four types of MLs. In 2000, scientists at NINDS laboratories and other research institutions identified the gene responsible for ML IV. This gene, MCOLN1, makes the protein mucolipin-1. Due to mutations in the gene, mucolipin-1 is missing or dysfunctional in people with ML IV. This important genetic finding allows for the accurate diagnosis of individuals as well as prenatal (before birth) diagnosis and the screening of carriers of the disease.

Prenatal diagnosis for ML is accomplished using a procedure known as chorionic villus sampling (CVS). It is usually done around the eight to 10th week of pregnancy and involves removing and testing a very small sample of the placenta. For ML types I, II, and III, placental cells called amniocytes are grown in culture and then tested to measure enzyme activity levels. For ML IV, no culture is required. DNA is obtained directly from the amniocytes and analyzed to find if mutations consistent with ML IV have occurred in the DNA. This technique is called genotyping.

Genetic testing for ML IV is available at specialized laboratories. Genetic counselors can help explain how the MLs are inherited and the effect of these diseases on individuals and their families. Counselors can also help adults who might have a defective gene decide whether or not they wish to have children. Psychological counseling and support groups for people with genetic diseases may also help individuals and their families cope with ML.

Treating ML

Currently, there is no cure or specific treatment for ML. Therapies are generally geared toward treating symptoms and providing supportive care to the child. For individuals with corneal clouding, surgery to remove the thin layer over the eye has been shown to reduce the cloudiness in the eye. However, this improvement may be only temporary. Physical and occupational therapy may help children with motor delays. Children with language delays may benefit from speech therapy.

Care also should be taken to maintain the overall health of individuals living with ML. For example, children at risk for failure to thrive (growth failure) may need nutritional supplements, especially iron and vitamin B12 for individuals with ML IV. Respiratory infections should be treated immediately and fully with antibiotics.

What are the latest updates on mucolipidoses?

The National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health (NIH), is the federal agency with primary responsibility for conducting and funding research on disorders of the brain and nervous system, including the MLs.

Discovery of the ML genes enabled NINDS researchers to study the genes' functions and will facilitate studies on drugs that may lead to effective treatments. In addition, investigators at grantee institutions are conducting studies on Caenorhabditis elegans, an animal model, which is frequently used to determine the effects of genetic mutations. Other grantees are using Drosophila, the fruit fly model, to study a mutation in the ML IV gene. And one of the research teams involved in the discovery of the ML IV gene is conducting further genetic studies to explore the normal and abnormal functions of the ML IV gene.

Learn About Clinical Trials
Clinical trials are studies that allow us to learn more about disorders and improve care. They can help connect patients with new and upcoming treatment options.

How can I or my loved one help improve care for people with mucolipidoses?

Consider participating in a clinical trial so clinicians and scientists can learn more about ML and related disorders. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of volunteers are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.

For information about participating in clinical research visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with ML at

Where can I find more information about mucolipidoses?

Information may be available from the following organizations and resources:

Order publications from the NINDS Catalog
The NINDS Publication Catalog offers printed materials on neurological disorders for patients, health professionals, and the general public. All materials are free of charge, and a downloadable PDF version is also available for most publications.