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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.

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

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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.

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

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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.

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Estimated at 1:100,000 live births.

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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.

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Galactosyl-3-sulfatide (cerebroside sulfate) is normally located on the surface of the myelin sheath, maintaining electrical neutrality, sodium transport, and opioid receptor function. It is hydrolyzed by the lysosomal arylsulfatase A with saposin B (a glycoprotein) as coenzyme. Enzyme deficiency leads to galactosyl sulfatide accumulation in myelin (demyelination), kidney (excess excretion), and gallbladder (cholecystitis). Rarely, saposin B deficiency causes metachromatic leukodystrophy.

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Clinical course. Biochemical: (a) Decreased arylsulfatase A activity in peripheral leukocytes and cultured skin fibroblasts; (b) increased sulfatide in cerebrospinal fluid and urine. Delayed nerve conduction and evoked potentials. Characteristic CT scan and MRI images show white matter lesions and cortical atrophy. Histology: Spherical metachromatic granules in the central and peripheral nervous systems (sural nerve). Prenatal and heterozygote diagnosis is possible.

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Progressive white matter disease, starting with gait disturbance, mental regression, and urinary incontinence. Congenital form results in early death. Late infantile form is usually recognized during the second year of life: common manifestations are progressive blindness, loss of speech, quadriparesis, posturing, peripheral neuropathy, and seizures. The disease process lasts 2 to 6 years. The juvenile form starts between 4 and 12 years. The adult form is slowly progressive with mental dysfunction, dementia, and behavioral problems. Multiple sulfatase deficiency is a rare form of metachromatic leukodystrophy, with features resembling mucopolysaccharidosis and ...

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