Mucolipidosis type IV (ML IV) is a lysosomal storage disease characterised clinically by psychomotor retardation and visual abnormalities including corneal clouding, retinal degeneration, or strabismus. The disease is rare in the general population but is more prevalent among Ashkenazi Jews, among whom the prevalence at birth is 1 in 40 000 corresponding to a frequency of heterozygotes of 1 in 100. First signs appear during the first year of life or later, but clinical progression is usually slow. In ML IV patients, phospholipids, gangliosides and mucopolysaccharides accumulate in lysosomal inclusions, some of which resemble membranous cytoplasmic bodies found in gangliosidoses. The condition seems to be caused by anomalies in the endocytosis of membrane components towards the lysosomes. It is transmitted as an autosomal recessive trait. The causative gene, MCOLN1, is located in the 19p13.3-p13.2 region and encodes mucolipin-1 (MLN1), a membrane protein from the transient receptor potential (TRP) channel family. Around 20 mutations have been described in the literature, two of which represent 95% of the alleles identified in the Ashkenazi population. Diagnosis may be suspected following detection of autofluorescence in fibroblasts cultured from ML IV patients and is confirmed by the identification of causative mutations in the MCOLN1 gene. Prenatal diagnosis is feasible through microscopic analysis of amniocytes or chorionic villus samples, or through molecular analysis in cases for which the genetic anomaly has been characterised in either the index case or the parents. To date, there is no specific therapy for the disease. Treatment is mainly symptomatic, targeted towards management of the visual manifestations and neurological handicap.
Last update: June 2006