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Mucolipidosis IV

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NORD is very grateful to Abraham Yu, NORD Editorial Intern from the University of Notre Dame, and Ehud Goldin, PhD, Section on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, for assistance in the preparation of this report.

Synonyms of Mucolipidosis IV

Disorder Subdivisions

General Discussion

Mucolipidosis IV is a rare metabolic disorder characterized by intellectual disability; severe impairment in the acquisition of skills requiring the coordination of muscular and mental activities (psychomotor retardation); diminished muscle tone (hypotonia); clouding (opacity) of the clear portion of the eyes through which light passes (cornea); and progressive degeneration of the nerve-rich membrane lining the eyes (retinal degeneration). Mucolipidosis IV is inherited as an autosomal recessive genetic trait and caused by mutations in the MCOLN1 gene.


The severe form of the disease is called typical mucolipidosis IV, and the mild form is called atypical mucolipidosis IV. Approximately 95 percent of individuals diagnosed with this condition have the severe form.

The symptoms and physical findings associated with mucolipidosis IV are usually apparent within three to eight months following birth. The first recognized symptoms are usually clouding (opacity) of the cornea and eye movement abnormalities. In some cases, these symptoms may be overlooked until three to five years of age.

Most affected infants exhibit hypotonia, moderate to severe intellectual disability, delays in reaching developmental milestones, and/or significant psychomotor retardation.

In addition, individuals with mucolipidosis IV may have abnormalities affecting the eyes including crossed eyes (strabismus), puffy eyelids, degeneration of the nerve-rich membrane lining the eyes (retina), and/or visual impairment (amblyopia) in an eye that appears structurally normal. In some cases, such eye abnormalities may result in an abnormal sensitivity to light (photophobia) and/or nearsightedness (myopia).

Individuals with mucolipidosis IV develop iron deficiency anemia because their stomachs do not secrete acid. They do not have enlarged livers or spleens, skeletal involvement, or mucopolysaccharides in the urine.

Patients exhibit accumulation of certain fatty substances (lipids) and certain complex carbohydrates (mucopolysaccharides) within the cells of many tissues of the body. Those appear as large vacuoles and fluorescent vesicles in patient cells.


Mucolipidosis IV is inherited as an autosomal recessive genetic trait. The responsible gene has been isolated and its protein-product, as well as its chromosomal location, determined. The gene, designated MCOLN1, has been tracked to 19p13.3-p13.2 where it encodes for the mucolipin-1 protein. Mutations in this gene result in a deficiency of transport channel receptor protein. The exact function of this protein is still unknown. The effect of mutations on patient and animal model cells indicates a loss of regulation on intracellular traffic which eventually affects various tissue functions.

Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as p and a long arm identified by the letter q. Chromosomes are further subdivided into bands that are numbered. For example, chromosome 11p15.4 refers to band 15.4 on the short arm of chromosome 11.

Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

Mucolipidosis IV is a rare inherited metabolic disorder that affects males and females in equal numbers. The disorder was first identified in 1974 and as of 2010, 70 cases have been reported in the medical literature. The precise incidence is unknown, but is estimated to be approximately 1:40,000. About 70% of those diagnosed are of Ashkenazi Jewish ancestry.

Related Disorders

Symptoms of the following disorders can be similar to those of mucolipidosis IV. Comparisons may be useful for a differential diagnosis:

Clinically the more severe cases of MLIV tend to be misdiagnosed as cerebral palsy, a group of developmental diseases with no known genetic cause. This can be easily corrected by testing blood gastrin level, which is increased in MLIV patient due to the inability to produce stomach acid. In milder cases the disease does not affect the development of children, but vision deteriorates with age and some aspects of eye abnormalities exist in the patients.

Laboratory testing, in particular microscopic examination of patient tissues reveal accumulation of large vacuoles in patient’s cells. This would be characteristic of mucolipidoses and mucopolysaccharidoses. The mucolipidoses are a subgroup of lysosomal storage disorders and include I-cell disease, pseudo-hurler polydystrophy, and mucolipidosis IV. I-cell disease (mucolipidosis type II) is characterized by diffused deficiency of lysosomal enzymes within the cell and is not associated with excretion of mucopolysaccharides in the urine. Pseudo-Hurler polydystrophy (mucolipidosis type III) is characterized by a deficiency of multiple lysosomal enzymes needed to break down mucopolysaccharides. ML III affects males more often than females, and can be identified by such symptoms as claw-like hands, somewhat coarse facial features, short stature and pain in the hands. Intelligence tends to be normal in most individuals, but mild intellectual disability is possible.

The mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders. Lysosomes function as the primary digestive units within cells. Enzymes within lysosomes break down or digest particular nutrients, such as certain carbohydrates and fats. In individuals with MPS disorders, deficiency or malfunction of specific lysosomal enzymes leads to an abnormal accumulation of certain complex carbohydrates (mucopolysaccharides or glycosaminoglycans) in the arteries, skeleton, eyes, joints, ears, skin, and/or teeth. These accumulations may also be found in the respiratory system, liver, spleen, central nervous system, blood, and bone marrow. This accumulation eventually causes progressive damage to cells, tissues, and various organ systems of the body. There are several different types and subtypes of mucopolysaccharidosis. These disorders, with one exception, are inherited as autosomal recessive traits. (For more information on these disorders, choose "mucopolysaccharidoses" as your search term in the Rare Disease Database.)

Free sialic acid storage disorders are a group of related disorders characterized by the abnormal accumulation of sialic acid in various cells and tissues of the body. These disorders are generally broken down into three subtypes: infantile free sialic acid storage disease (ISSD), the most severe form; Salla disease, the mildest form; and intermediate Salla disease which is less severe than ISSD, but more serious than Salla disease. The specific symptoms associated with these disorders can vary greatly. All the disorders are characterized by some degree of degeneration of nerve cells (neurodegeneration) and cognitive impairment. Free sialic acid storage disorders occur because of mutations of the SLC17A5 gene and are inherited in an autosomal recessive fashion. (For more information on these disorders, choose "free sialic acid storage disorders" as your search term in the Rare Disease Database.)

Standard Therapies

Mucolipidosis IV may be suspected based upon a thorough clinical examination, a detailed patient history, and a variety of specialized tests. Individuals with mucolipidosis IV present with iron deficiency anemia, high serum gastrin levels and characteristic findings on brain MRI examinations. In most cases, an electron microscope is used to visualize characteristic lysosomal storage bodies in fibroblasts obtained from biopsied tissue of the skin and/or the delicate membrane that lines the eyes (conjunctiva). Molecular genetic testing for mutations in the MCOLN1 gene is available to confirm the diagnosis.

Treatment of mucolipidosis IV is symptomatic and supportive. Symptoms associated with clouding of the corneas may be treated by the use of contact lenses and/or artificial tears. Intense physical, occupational and speech therapy are also of benefit. Iron replacement is utilized for those with anemia.

Genetic counseling is recommended for affected individuals and their families.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

For information about clinical trials conducted in Europe, contact:

Organizations related to Mucolipidosis IV


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Report last updated: 2014/05/22 00:00:00 GMT+0