Metachromatic leukodystrophy (MLD) is a rare autosomal recessive leukodystrophy, which means both copies of the affected gene in each cell have mutations.
The parents of an individual with this disease usually each carry one copy of the mutated gene, but do not show signs and symptoms of the condition. The affected gene is called ARSA, which provides instructions for producing an enzyme called arylsulfutase A. Deficiency of this enzyme results in accumulation of a fat, referred to as sulfatides in cells. A few individuals with MLD have mutations in the PSAP gene. In some cases, individuals with very low arylsulfatase A activity show no symptoms. This condition is called pseudoarylsulfatase deficiency.
There are late infantile, juvenile, and adult forms. About 75 percent of patients have the late infantile or juvenile forms equally divided between them. Twenty-five percent have the adult form.
The late infantile form manifests between 6 months and 4 years of age, and starts with unsteady gait and gradual loss of the ability to walk, and mental decline. Speech deteriorates and children may slur or have difficulty finding the right words. While muscle tone is initially decreased, over time, patients develop muscle stiffness. Feeding difficulties and episodes of airway obstruction occur. About 25 percent of patients develop seizures. Death usually occurs about five years after onset of clinical symptoms.
In the juvenile form, the age of onset ranges from 4 to 16 years. Patients show gradual deterioration in school performance, slurred speech, clumsy gait, and incontinence. They may also have emotional or behavioral disturbances. Within a year, spastic paresis develops, and the child loses the ability to walk. Seizures occur in 50 percent of patients. The illness progresses to complete loss of function, and most patients die before age 20.
Onset of the adult form of MLD has been reported at various ages up to the sixties. Patients show a gradual decline of intellectual abilities. They become emotionally labile, and show memory deficits, disorganized thinking, behavioral abnormalities, or psychiatric symptoms like hallucinations or delusions. They also experience clumsiness of movement, and urinary and sometimes fecal incontinence.
While limited data exists, transplantation of bone marrow or cord blood-derived hematopoietic stem cells may have a beneficial effect. Gene therapy trials have been successful in animal models of MLD.