Metachromatic Leukodystrophy (MLD) is a nervous system disorder affecting the myelin sheath that protects nerve cells.
The deficiency of the enzyme arylsulfatase A leads to the accumulation of a harmful substance, destroying the myelin sheath and impairing brain and nerve functions. MLD comes in three forms: infantile (common, symptoms start in early childhood), juvenile (symptoms arise after age 3 but before adolescence), and adult (symptoms appear after puberty). Symptoms include muscle stiffness, seizures, and progressive loss of functions. While there’s no cure, treatments manage symptoms with medications, physical therapy, and supportive devices. Bone-marrow transplantation is an option for some, but it has risks and is not a guaranteed cure. Most treatments focus on improving the quality of life for individuals with MLD.
MLD is caused by pathogenic (disease-causing) variants in the ARSA gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Ashkenazi Jewish descent have a 1 in 823 chance to be a carrier, but individuals of Sephardic Jewish decent have a 1 in 46 chance to be a carrier.
Other names for this condition are arylsulfatase A deficiency disease, cerebral sclerosis, diffuse, metachromatic form, cerebroside sulphatase deficiency disease, Greenfield disease, sulfatide lipidosis, and sulfatidosis.