Mucolipidosis IV (MCOLN1)
Mucolipidosis IV is an autosomal recessive disorder caused by pathogenic variants in the gene MCOLN1. It is predominantly diagnosed in individuals of Ashkenazi Jewish descent, although it has also been reported in patients of other ethnicities. The typical form of the disease is characterized by a severe motor delay (which halts at the level of a 1 or 2 year old) and vision loss as a result of retinal degeneration and corneal clouding. Most patients do not learn to speak or walk, but may learn some sign language or be able to sit independently. Patients are intellectually disabled and have difficulty controlling their movements. Approximately 15% of patients experience deterioration of neurological symptoms over time, but the neurologic deficits do not change in the remainder of patients. About 5% of patients have a milder, atypical form characterized by progressive ataxia and eye abnormalities, and they may learn to walk. Most patients live into adulthood, although life expectancy is shorter than normal. Specific variants have been associated with typical or atypical disease, and therefore it may be possible to predict the severity of disease based on the genotype. The pathogenic variant common in the Ashkenazi Jewish population is associated with the more severe form.
For information about carrier frequency and residual risk, please see the residual risk table.