This article describes the characteristics, pathophysiology, symptoms, and treatment of Mucolipidosis IV.
Introduction
Mucolipidosis (ML) IV is one of four types of the disease, each of which is classified according to enzyme mutation or deficiency. While ML I, II, and III do not disproportionately affect any particular racial or ethnic group, ML IV has a high carrier rate amongst Ashkenazi (Eastern European) Jews, with a carrier frequency between 1 in 90 and 1 in 100. ML is a rare genetic disease that prevents the body from producing a sufficient amount of the roughly 40 to 50 enzymes responsible for the normal functioning of lysosomes. Lysosomes, in turn, are responsible for breaking down carbohydrates and fatty substances so the body can use them for metabolic functions. When these excess carbohydrates and fats are not broken down they accumulate in bone marrow, as well as muscle, nerve, and liver tissue, instead of being transported to the parts of the body where they are needed.
Pathophysiology
ML IV is triggered by mutations in the non-selective cation channel TRPML1. While researchers understand that mutations in TRPML1 inhibit lysosomal storage, they do not know exactly how this leads to neurodegeneration. However, some researchers think TRPML1 channels iron ions, so when it malfunctions, the result is cellular iron deficiency.
Symptoms
Symptoms range from mild to severe, and they can be present at birth, or they can develop over time. Two of the most common symptoms exhibited in children with ML IV include severely delayed psychomotor development and impaired vision due to corneal clouding and retinal degeneration. Most individuals afflicted with ML IV are unable to walk independently or talk using more than a few words. Some are able to sit independently, crawl, and use a limited amount of sign language to communicate. Other symptoms include a failure to thrive, increased risk of respiratory infections, and poor mental capacities.
Prognosis and Treatment
There is no cure for ML at this point in time, so treatment is limited to alleviating ML symptoms. Children with the disorder benefit from physical therapy and speech therapy, as well as B12 and iron supplements if they exhibit a failure to thrive. A temporary solution to corneal clouding is surgery; this is a stopgap measure, however. Depending on the nature and severity of their symptoms, some ML sufferers also benefit from ankle-foot orthotics, eye drops and/or artificial tears, and anti-epileptic medications.
This post is part of the series: The Ashkenazi Jewish Genetics Panel
This series describes the diseases tested for in the Ashkenazi Jewish Genetics Panel (AJGP).
