Deficiency, sphingomyelinase

Also called Niemann-Pick disease, this is a disorder of the metabolism of a lipid (fat) called sphingomyelin that usually causes the progressive development of enlargement of the liver and spleen (hepatosplenomegaly), "swollen glands" (lymphadenopathy), anemia and mental and physical deterioration. Niemann-Pick disease is hereditary and follows an autosomal recessive pattern. The parents are carriers of one copy of the gene and each of their children, boys and girls alike, has a 1 in 4 (25%) chance of receiving both of the parents' genes for Niemann-Pick and manifesting the disease. The onset of the classical form of Niemann-Pick disease is in very early infancy and death is usually before age 3. The lipid accumulates in cells (called reticuloendothelial cells) in the liver and spleen and other cell types throughout the body including the nerve ganglion cells of the central nervous system. The neurological features of Niemann-Pick disease include mental retardation, spasticity, seizures, jerks, eye paralysis (ophthalmoplegia) and ataxia (wobbliness). Physical growth is retarded. The gastrointestinal features include hepatosplenomegaly, jaundice, hepatic (liver) failure, and ascites (fluid in the abdomen). Eye hallmarks of Niemann-Pick disease include the "cherry red spot" in the macula in the center of the retina, opacity of the cornea and brown discoloration of the lens capsule. Respiratory problems include pulmonary infiltration. Coronary artery disease occurs early. There is easy bruising. The sphingomyelin accumulation is due to deficiency of the enzyme sphingomyelinase. The gene for this enzyme and hence the location of the gene for this disease is in chromosome band 11p15.4-p15.1. Typical cells (called Niemann-Pick cells) that have a foamy appearance due to their storage of sphingomyelin are found in the bone marrow, spleen and lymph nodes. These unusual cells help in establishing the diagnosis. At least 5 forms of Niemann-Pick disease have been distinguished: the classical infantile form (type A), the visceral (organ) form (type B), the subacute or juvenile form (type C), the Nova Scotian variant (type D), and the adult form (type E). The disease is named for the German physicians Albert Niemann (1880-1921) and Ludwig Pick (1868-1944). Other names for the disease include sphingomyelinase deficiency.