SNP Shot: Genomic Insights

Metachromatic leukodystrophy (MLD) is a genetic disease where fats called sulfatides build up in the body's cells. This buildup is particularly damaging to cells in the nervous system that make myelin. Myelin is a protective coating around nerve cells, and these coated cells form white matter. In MLD, sulfatides accumulate in myelin-producing cells, leading to the progressive destruction of white matter (leukodystrophy) throughout the nervous system. This includes the brain and spinal cord (central nervous system) and the nerves that connect them to muscles and sensory cells (peripheral nervous system).

The white matter damage in MLD causes a gradual decline in mental abilities and motor skills, like walking. Affected individuals also experience numbness and tingling in their limbs (peripheral neuropathy), loss of bladder control (incontinence), seizures, paralysis, inability to speak, blindness, and hearing loss. Eventually, they become unaware of their surroundings and unresponsive. While the main problems are neurological, sulfatide buildup can also affect other organs, most commonly the gallbladder.

The most common type of MLD is the late infantile form, affecting 50-60% of people with the condition. It usually starts in the second year of life. Children with this form lose any speech they've learned, become weak, and have trouble walking (gait disturbance). The condition worsens over time, with muscle tone usually decreasing first, then increasing to the point of stiffness. Children with the late infantile form typically don't live past childhood.

Another form of MLD, the juvenile form, affects 20-30% of individuals. It starts between ages 4 and adolescence. The first signs may be changes in behavior and increasing difficulty with schoolwork. This form progresses more slowly than the late infantile form, and affected individuals may live for about 20 years after diagnosis.

The adult form of MLD affects about 15-20% of individuals. Symptoms begin in the teenage years or later. Often, the first signs are behavioral problems such as alcohol or drug abuse, or difficulties at school or work. Psychiatric symptoms like delusions or hallucinations may also occur. People with the adult form may survive for 20 to 30 years after diagnosis, with periods of relative stability interspersed with periods of more rapid decline.

Metachromatic leukodystrophy's name comes from how cells with built-up sulfatides look under a microscope. The sulfatides form granules that are "metachromatic," meaning they stain differently than the surrounding cell material when prepared for viewing.

Inheritance:

MLD is an autosomal recessive genetic disorder. This means that a person must inherit two copies of the mutated gene, one from each parent, to develop the condition. The parents typically do not have any symptoms of the disorder themselves.