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
Arylsulfatase A Deficiency; Cerebroside Sulfatase Deficiency; Diffuse Cerebral Sclerosis; Greenfield Disease; Sulfatide
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
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.
Estimated at 1:100,000 live births.
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, 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
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.
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 ...