Neuronal Lipidoses

These diseases are inherited in an autosomal recessive mode except for the Fabry's disease, which has an X-linked recessive inheritance. They affect chiefly infants and children and may also occur in juveniles and adults. The diseases display both similar and distinctive clinical features. Generally, infantile diseases with onset at 6 months to 2.5 years manifest with loss of already acquired psychomotor skills, growth retardation, visual impairment, and often seizures. Death occurs within 1 to 3 years of onset. Juvenile diseases with onset at 4 to 8 years of age manifest with combinations of pyramidal, extrapyramidal, and cerebellar symptoms and signs; behavioral changes; and mental decline. The clinical course may range from 10 to 15 years. Adult-onset diseases present with psychiatric symptoms, cognitive decline, and variable neurologic signs. The clinical course is protracted, averaging 15 to 20 years. The diagnosis requires enzyme assays complemented by ancillary tests (see Table 9.1). In several diseases, magnetic resonance imaging (MRI) demonstrates abnormalities in basal

TABLE 9.2.

Lysosomal Enzy

me Deficiencies with

Systemic Lipid Storage

Diseases

Deficient Enzymes

Stored Products

GM1

ß-Galactosidase

GM1 Galactoside

Gangliosidosis

Oligosaccharides

Keratan sulfate

Niemann-Pick

Sphingomyelinase

Sphingomyelin

disease

Gaucher's disease

Glucocerebrosidase

Glucocerebroside

Farber's disease

Ceramidase

Ceramide

Fabry's disease

a-Galactosidase

Trihexosyl

glycolipids

Wolman's disease

Acid lipase

Triglycerides,

cholesteryl

Ballooned cortical pyramidal neuron, a histologic hallmark of storage diseases. The perikaryon is large, pear shaped. The nucleus and some residual Nissl substance are displaced toward the apical dendrite.

ganglia and thalamus in the early stage and cortical and white matter atrophy in the late stage.

The lipids involved in neuronal lipidoses are the sphingolipids: sphingomyelin, cerebrosides, and gangli-osides, all normal constituents of the neurons. They have in common a ceramide moiety (derived from the amino alcohol sphingosine) attached to a long-chain fatty acid. The deficiency of a specific enzyme blocks the degradation of its lipid, which then accumulates in excessive amounts in the perikaryon of the neurons, first hindering their function and eventually leading to their disintegration. The neuronal storage is widespread in the central, peripheral, and autonomic nervous systems. Ballooned neurons filled with storage material are his-tologic markers (Fig. 9.1). A number of diseases are multisystemic. In these, the retina and the visceral organs, chiefly the liver and spleen, participate in the storage process (Table 9.2).

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