A ganglioside biosynthesis disorder caused by (N-acetylneuraminyl)- galactosylglucosylceramide N-acetyl transferase (E.C. 2.4.192) deficiency with excessive accumulation of ganglioside GM3 in the liver and brain tissue and absence of higher ganglioside homologs. Clinical features include limpness, retarded psychomotor development, coarsening of facial features, macroglossia, gingival hypertrophy, hepatosplenomegaly, inguinal hernia, and stubby hands and feet. Most patients die in infancy."
GM3 gangliosidosis is also called hematoside sphingolipodystrophy. Knowledge of clinical symptoms is based on the description of only one patient. Respiratory difficulties, generalized seizures, lethargy, feeding difficulties, gingival hypertrophy, macroglossia, a coarse facies, dry, thickened and hirsute skin, and broad hands and feet were all apparent immediately at birth or soon thereafter. The child was hypotonic, and reflexes were decreased. Inguinal and umbilical hernias were found. The liver and spleen were firm and enlarged. Death occured after a few months due to recurrent bronchopneumonia.
A one month old male (JH) was first seen because of poor physical and motor development, frequent seizures, and an unusual appearance. The first child of young, unrelated Jewish parents, JH weighed 7 1bs. 12 oz. at birth after a normal 8 mo. gestation. He was limp and unresponsive, with coarse facies, macroglossia, gum hypertrophy, squat hands and feet, flexor contractures of the fingers, thickened loose hirsute skin, large inguinal hernia, enlarged liver and spleen and normal fundi. Death at 3 1/2 months followed a series of bronchopneumonic episodes. These features suggested GM1, gangliosidosis, which was ruled out by the finding of normal β-galactosidase activity in leukocytes and in a liver biopsy. The activities of acid phosphatase, β-glucosidase, β-N-acetylhexoseaminidase,α-fucosidase, α-mannosidase, and arylsulfatase A were greater than normal. The diagnosis of GM3 gangliosidosis was established by thin-layer chromatographic analysis, which demonstrated the accumulation of GM3(N-acetylneuraminylgalactosylglucosylceramide) in post mortem samples of brain and liver. The enzymatic basis of the GM3 storage is now under investigation. (Supported in part by the John A. Hartford Fndn. and the Tay-Sachs Assn. of Maryland.)