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Mucolipidosis IV

Last updated: 2003-09-11

Mucolipidosis IV (ML IV), first described in 1974, is among the most recently recognized Jewish genetic diseases. To date, over 70 patients, most of Ashkenazi descent, have been reported.

Children with ML IV appear normal at birth but develop signs of central nervous system deterioration during the first year of life. Sitting is delayed and most people with ML IV do not walk. Motor and mental retardation are usually mild to moderate, and are slowly progressive. Some patients may become more severely retarded in the second or third year of life. One of the earliest signs of ML IV is an eye problem referred to as corneal clouding, but approximately 30% of persons with ML IV do not develop corneal clouding until between three and five years of age. Other eye findings may include strabismus (crossed eyes), and retinal degeneration, which if it develops may lead to blindness in later years. Individuals affected with ML IV currently range from 1 to 30 years of age. Prognosis beyond this age and life expectancy are not known. Recently, a few very mildly affected individuals with ML IV have been described, which raises the possibility of other mildly affected but undiagnosed individuals.

The name, Mucolipidosis IV, derives from the presence of diagnostic storage bodies (cells with a characteristic appearance that can be seen using an electron microscope) in almost every cell of affected patients. The storage bodies contain incompletely broken down materials, known as lipids, due to either an enzyme abnormality or deficiency. Similar storage bodies are observed in related disorders known as the mucopolysaccharidoses and lipid storage diseases. Thus, the designation Mucolipidosis. The diagnosis should be considered in mildly to moderately retarded Ashkenazi Jewish children who have corneal clouding. The demonstration of the characteristic storage bodies in a skin biopsy supports the clinical diagnosis.

The disease is inherited in an autosomal recessive manner. When a child is born with ML IV, it indicates that both parents are carriers of the disease. Carriers themselves are unaffected, but carrier couples have a 1 in 4 (25%) chance in each pregnancy to have an affected child. In September of 2000, researchers from Israel reported the identification of the Mucolipidosis type IV gene (also referred to as the MCOLN1 gene) on chromosome 19. The investigators found three mutations in the gene, although it is likely that additional mutations will be identified in the future. Of the three mutations reported thus far, two appear to account for over 95% of MLIV among Ashkenazim.

Prior to these recent findings, prenatal diagnosis for MLIV was available only for couples who already had an existing family history of the disease. Carrier testing was not possible, even for family members at risk of having a child with MLIV. As a result of the identification of the gene mutations, it is now possible to offer highly accurate carrier testing and prenatal diagnosis for MLIV, both for families with a previous history of the disease and for all couples of Ashkenazi Jewish ancestry.