ARSA

The ARSA gene provides instructions for making the enzyme arylsulfatase A. This enzyme is located in cellular structures called lysosomes, which are the cell's recycling centers. Within lysosomes, arylsulfatase A helps process substances known as sulfatides. Sulfatides are a subgroup of sphingolipids, a category of fats which are important components of cell membranes. Sulfatides are abundant in the nervous system's white matter, consisting of nerve fibers covered by myelin. Myelin, made up of multiple layers of membranes, insulates and protects nerves.

metachromatic leukodystrophy - caused by mutations in the ARSA gene

More than 60 mutations that cause metachromatic leukodystrophy have been identified in the ARSA gene. These mutations greatly reduce the activity of arylsulfatase A. Severe disruption in arylsulfatase A activity interferes with the breakdown of sulfatides. As a result, these substances can accumulate to toxic levels in the nervous system. The buildup of sulfatide gradually destroys the cells forming the myelin sheath, the covering that protects nerves and promotes the efficient transmission of nerve impulses. Destruction of the myelin sheath (demyelination) leads to the loss of white matter (leukodystrophy) and impairment of nervous system function, resulting in the signs and symptoms of metachromatic leukodystrophy.

In some cases, individuals with very low arylsulfatase A activity show no signs or symptoms of metachromatic leukodystrophy. This condition is called pseudoarylsulfatase deficiency, and seems to be caused by specific variations of the ARSA gene. These variations may be present in as many as 5 to 10 percent of European and North American populations.