JUVENILE GM2 GANGLIOSIDOSIS (AMB VARIANT) - INABILITY TO ACTIVATE HEXOSAMINIDASE-A BY ACTIVATOR PROTEIN

  • 1 January 1983
    • journal article
    • research article
    • Vol. 35  (4) , 551-564
Abstract
Two siblings from a consanguineous Puerto Rican marriage were found to have a juvenile-onset type of lipidosis first noted at age 2.5 by expressing difficulties with motor function and developmental delay. They continued to deteriorate, showing muscle atrophy, spasticity and loss of speech, and death occurred at ages 7 and 8. Examination of the brains from these patients revealed that the concentration of GM2 ganglioside was .apprx. 56% of the total gangliosides. Hexosaminidase and percent hexosaminidase A (HEX A) and other lysosomal enzymes were normal in cultured skin fibroblasts, liver and brain. The concentration of the activator protein required for the enzymatic hydrolysis of GM2 ganglioside was in high normal levels in the brain of the patient available. The HEX A from the patient''s brain and liver as well as from skin fibroblast lysates could not be activated to hydrolyze GM2 ganglioside by the activator protein from a control or himself. The HEX A from a control could be activated by the activator protein from controls or this patient. These patients appear to have a defect in HEX A, which does not affect its heat stability, electrophoretic migration and activity toward fluorogenic substrates, but may affect the binding of the activator protein required for GM2 ganglioside hydrolysis. These patients can be called the AMB variant of GM2 gangliosides to denote the mutation in HEX A but with normal levels of HEX A and B with synthetic substrates. This is to distinguish these patients from those missing the activator protein and normal HEX A and B levels.