As a group, the sphingomyelinoses, which are disorders of autosomal recessive inheritance, are marked by prominent organomegaly and delayed motor and mental development. Sphingomyelin is a molecule containing a ceremide, a phosphoric acid ester, and choline.
There are four types of sphingomyelinoses or Niemann- Pick disease (types A, B, C, D, and E), all of which have neurological involvement except types B and E. Approximately 50 percent of affected patients belong in the type A group, characterized by severe neurological symptoms. Although type C disease involves moderate neurological signs, often extrapyramidal in nature, type D has only mild neurological sequelae that appear later in the course. Type B has no neurological signs. All of the sphingomyelinoses are transmitted as autosomal recessive traits (...lable 30:.3.).
In all cases, generally the first observed clinical abnormality is hepatosplenomegaly. In addition to the systemic organopathy, patients develop progressive neurological deterioration with motor and mental decline. Macular degeneration occurs, and a cherry-red spot appears in about 25 percent of patients with type A disease, usually in the first year of life. Seizures may develop, and as the disease progresses, children become inexorably obtunded and difficult to feed. Recurrent infection is often a major problem, and death occurs before 2 years of age. In some cases, peripheral nervous system involvement is detected with slow nerve conduction velocities. In type C disease, the childhood or adult form, deterioration occurs more slowly, and the patients usually seem normal until 2 years of age or even young adulthood. They often develop dystonia with selectively swollen cells in the basal ganglia. In such patients, foamy histiocytes can be found in bone marrow and spleen, and hepatic cells show small clusters of histiocytes that resemble sea-blue histiocytes. y In type D disease, neurological difficulties usually begin between the second and fourth years of age, related predominantly to hepato- splenopathy. y
The differential diagnosis rests with the other storage diseases, but in the absence of neuronal ceroid-lipofuscins and ganglioside, hepatosplenomegaly should strongly suggest the sphingolipidoses. Most confusion in diagnosis involves the cerebrosidoses. Definitive diagnosis is based on identifying excessive amounts of sphingomyelin and the foamy cells. Antenatal diagnosis of types A and B disease can be made. Most histological information has been obtained from studies of the infantile or type A form. Very often the central nervous system of these patients is gliotic, small, and atrophic. The gray matter shows necrotic changes with large neurons that are distended and ballooned with apparent storage of sphingomyelin. In some patients, there are extensive abnormalities in the spinal cord, midbrain, and cerebellum. The white matter is rarely affected. Changes in retinal cells similar to those in the brain are seen. Biochemical assay of membranous cytoplasmic bodies reveals large amounts of sphingomyelin and cholesterol.
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