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At a glance

It is an inherited disorder of the myelin metabolism with progressive loss of white matter in the central and peripheral nervous system. It is the most common form of leukoencephalopathy and is characterized by sulfatide accumulation in the brain and other areas of the body (liver, gall bladder, kidneys, and/or spleen). Clinical manifestations may include seizures, behavioral changes, spasticity, progressive dementia, psychomotor dysfunction leading to paralysis, and visual impairment leading to blindness. Metachromatic leukodystrophy (MLD) is part of a spectrum of diseases called leukodystrophies that results from a defect in lysosomal storage and consequently causes anomalies in sphingomyelin in the central nervous system.


Arylsulfatase A Deficiency; Cerebroside Sulfatase Deficiency; Diffuse Cerebral Sclerosis; Greenfield Disease; Sulfatide Lipidosis; Sulfatidosis.


There are three types of MLD described and consists of:

  • Late Infantile Metachromatic Leukodystrophy: Characterized by onset usually in the second year of life, most commonly before age 30 months. It is associated with rapid progression leading to death before age 5 years in most cases. The clinical features include psychomotor disturbances, spasticity, mental deterioration, progressive blindness, hypotonia, ataxia, and seizures. The cerebrospinal fluid contains elevated protein.

  • Juvenile Metachromatic Leukodystrophy: Typically begins between the ages of 4 and 10 years, presenting symptomatology similar to the late infantile form.

  • Adult Metachromatic Leukodystrophy: Begins after age 16 years with severe psychiatric behavioral disorders by age 30 years. Abdominal distension, dysarthria, loss of previously acquired intellectual skills, behavioral abnormalities, and dementia are particularly pronounced in this form of the disease.


The incidence of MLD is estimated between 1:40,000 and 160,000 individuals worldwide. The prevalence is significantly greater in certain isolated populations. The frequency is reported to be 1:75 Habbanites (a small group of Jews who immigrated to Israel from southern Arabia), 1:2,500 in the western portion of the Navajo Nation, and 1:8,000 among Arab descent that live in Israel. It is suspected that its inheritance is as an autosomal recessive trait, in which case an incidence of 1:40,000 equates to a carrier frequency of 1:100 in the general population. It is estimated that more than 3,600 newborns are affected with the disease every year, with 1,900 alive in the United States, 3,100 in Europe, and 49,000 alive worldwide. However, MLD is considered a rare disease in the United States.

Genetic inheritance

Autosomal recessive. Gene locus: long arm (q13) of chromosome 22 codes for the arylsulfatase A gene (3.2 kb). Gene mutations can lead to low (group A) or absent (group I) enzyme activity with the following phenotypes: late infantile (alleles II), juvenile (IA), and adult (AA). The saposin B gene is located on chromosome 10.


Galactosyl-3-sulfatide (cerebroside sulfate) is normally located on the surface of the myelin sheath, ...

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