Group of rare inherited disorders of fat metabolism.
Clinical features include jaundice, progressive loss of motor skills,
feeding difficulties, learning disabilities, and hepatosplenomegaly.
Lysosomal storage disorder caused by a defect in sphingolipid metabolism and
involving brain and/or viscera. There are five types of Newman-Pick disease.
Lipid Histiocytosis; Sphingomyelinase Deficiency.
Disorders of sphingomyelin storage were initially
grouped together under the eponym Niemann-Pick disease and classified as A,
B, C, D, E, and F. However, only types A and B are deficient in
sphingomyelinase; types C and D are biochemically and genetically different.
Types E and F are not well described. A new nomenclature has been proposed
that groups types A and B as type I and types C and D as type II, but this is not yet
universally adopted. Types A and B: Deficiency in sphingomyelinase. Types C and D: Basic defect not yet
Types A and B: The gene for lysosomal sphingomyelinase is located on chromosome
11p15.1-p15.4. Three mutations have been identified in Ashkenazi Jews
carrying type A. Other mutations cause type B phenotype and are found in
southern Europe and in the Mediterranean region.
Types C and D: The NPC1 gene on chromosome 18q11-12 is Niemann-Pick disease type C1 gene
(found worldwide) and mutated in type D (called Nova Scotia variant because of the high
incidence in the province of Nova Scotia, Canada); another gene, NPC2, has been identified.
Types A and B: Sphingomyelin accumulates in the brain, viscera,
and reticuloendothelial system. Types C and D: Still unknown but there is accumulation of
unesterified cholesterol and glucosylceramide in lysosomes. Sphingomyelinase
activity is normal in most tissues but is partially deficient in
fibroblasts. In the brain, this anomaly leads to swelling of the proximal
neurite segment in the cerebral cortex and accumulation of paired helical
filaments, as reported in Alzheimer disease.
Sphingomyelinase assay in leukocytes or in fibroblasts
shows residual activity that tends to be higher in type B than in type A.
Cultured fibroblasts obtained from skin biopsy allow staining with filipin to demonstrate
Type A: Infantile type. Sphingomyelin accumulates mainly in the brain. Starts with
feeding difficulties, hepatomegaly. Respiratory infections are common, with
a chest radiograph similar to that seen in miliary tuberculosis. Neurologic
deterioration in the second part of the first year of life, with loss of
contact, hypotonia, and spastic paresis. In 50% of cases, a cherry-red
spot is seen in the macula; it is a normal macula surrounded with
grayish-colored retina caused by storage compounds. Vacuolized lymphocytes
are found in the blood, and foam cells are present in the bone marrow.
Anemia and thrombocytopenia are late signs. Death usually occurs by age 3 years. No
Type B: Chronic form. Unlike type A, sphingomyelin accumulates mainly in the
viscera and reticuloendothelial system. It presents as hepatosplenomegaly or