A New Variant of Sandhoff's Disease

Abstract

ExtractA 28-month-old Negro male with atypical Sandhoff's disease (GM2 gangliosidosis, type 2) is described. Clinical presentation closely resembled Sandhoff's disease. The appendiceal neuron cytoplasm was distended with periodic acid-Schiff (PAS)-positive material. Hepatic glycolipid N-acetylneuraminic acid was elevated 1.5-fold, chiefly because of increased GM2. Neutral glycolipid hexose was elevated twofold, mainly because of a component with globoside-like chromatographic properties. Unlike patients with Sandhops disease, the child had total 0-D-N-acetylhexosaminidase activity 20-24% of normal in serum and plasma and 7-1 1% of normal in leukocytes and cultured fibroblasts, but activity in liver (<2y0 of normal) was similar to that in Sandhoff's disease. In all tissues examined, >95% of the activity was heat denaturable, corresponding in electrophoretic mobility to the heat-denaturable component of normal tissues. The decrease in heat-denaturable activity with time and the pH optimum were similar in patient and control crude tissue preparations and partially purified preparations of plasma hexosaminidase A. In the child's mother, total hexosaminidase activity was approximately 50y0 of mean control values in serum, plasma, and leukocytes, and serum hexosaminidase A was relatively increased. This finding, together with the death of at least three other children in the kindred from an apparently phenotypically similar illness, indicates the inherited nature of the disorder. SpeculationAppreciable hexosaminidase activity in serum and plasma and its marked deficiency in liver suggest that the active form (or forms) in serum and plasma differ from those in solid tissues, and that the mutation in the case described has altered the hexosaminidases in a manner that virtually abolishes their activity in solid tissues but permits their partial activity in serum and plasma.

The Natural History of Juvenile or Subacute GM2 Gangliosidosis: 21 New Cases and Literature Review of 134 Previously Reported

“…Optic atrophy was described in 10 patients during the course of the disease (15.4%). 11,13,24,35,36,38,42,64 Two patients had optic atrophy and macular alterations. 34,36 Four patients (4.6%) presented with macular alterations described as cherry-red spots.…”

Tay-Sachs Disease with Altered β-Hexosaniinidase B: A New Variant?

“…These variants may be due to allelic mutation o r double mutations in loci concerned with Hex isozymes (3, 5 , 10, 20, 21, 25, 26). Variant types .which have been reported may be divided into three groups: ( 1 ) the enzyme activities are present to a natural substrate but absent to a synthetic one (5,10,25), ( 2 ) the reversed condition as in the case of ( 1 ) (3,20), and ( 3 ) non-uniform distribution of the enzyme in various tissues in a single person (21,25,26).…”

Succinyl-CoA:3-ketoacid coenzyme A transferase (SCOT): Development of an antibody to human SCOT and diagnostic use in hereditary SCOT deficiency

“…The utilization of ketone bodies is mediated by two enzymes, succinyl-CoA:3-ketoacid CoA transferase (SCOT, EC 2.8.3.5) which catalyzes CoA transfer from succinyl-CoA to acetoacetate, and mitochondrial acetoacetyl-CoA thiolase (T2, EC 2.3.1.9). Hereditary deficiency of either SCOT (McKusick catalogue number 245050) [2] or T2 (McKusick catalogue number 203750) results in reduced ketolytic capacity, which manifests clinically by intermittent ketoacidotic attacks [3][4][5][6][7][8][9][10].…”

“…In unexplained hyperketotic states the analysis of organic compounds in plasma and urine does not allow a specific diagnosis for SCOT deficiency, although persistent hyperketonemia is believed to be characteristic of SCOT deficiency [3][4][5][6][7][8]. The assay of enzymatic activity is tedious and mutation analysis is expensive and should be limited to samples where SCOT is known to be deficient.…”