What is Mucolipidosis Type IV?

Mucolipidosis type IV is an inherited metabolic disorder characterized by developmental delay and impaired vision. There are two forms of Mucolipidosis type IV, categorized by the severity of signs and symptoms: 1. Typical mucolipidosis type IV This form is more severe and more commonly observed among people of Ashkenazi Jewish descent. The age of onset is usually before the age of one. Typical symptoms include delayed mental and motor skills development, intellectual disabilities, impaired speech and weak muscle tone that can lead to muscle spasticity (stiffness). Vision, although normal at birth, can progressively deteriorate with clouding of the cornea and breakdown of the retina over time, leading to severe vision loss or blindness in the teens. Progressive renal failure, iron deficiency and achlorhyria (impaired production of stomach acid) may also develop in affected people with this form of the disease. 2. Atypical mucolipidosis type IV This form is milder compared to the typical form, and is much less commonly observed in the general population. Symptoms are less severe and individuals affected with this form usually experience mild developmental delay, mild eye abnormalities and achlorhydria. Mucolipidosis type IV is caused by a mutation in the MCOLN1 gene, which encodes the mucolipin-1 protein. Mucolipin-1 is associated with transport of lipids and proteins between lysosomes and endosomes. It is also thought to be critical for brain and eye development, and normal functioning of stomach cells for digestive acid production. Mutations in the MCOLN1 gene can either inhibit protein production or result in non-functional protein. Two specific mutations in the MCOLN1 gene (delta 6.4kb and IVS3-2A>G) that are commonly found in people of Ashkenazi Jewish background, result in short, non-functional mucolipin-1. Without functional mucolipin-1, lipid and protein transportation are impaired, resulting in accumulation of these molecules in the lysosomes, leading to characteristic features observed in people with Mucolipidosis type IV. References: Jose CP, Ferreira MD, Schreiber-Agus N, Carter SM, Klugman S, MDa, Gregg AR, Gross SJ (2014). Carrier testing for Ashkenazi Jewish disorders in the prenatal setting: navigating the genetic maze. American Journal of Obstetrics and Gynecology. 211(3): 197-204. Schiffmann R, Grishchuk Y, Goldin E (2005)
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