Saccharopinuria

Description

Saccharopinuria, also known as hyperlysinemia type II, is an autosomal recessive metabolic condition with few, if any, clinical manifestations. Hyperlysinemia type II and hyperlysinemia type I (238700) both result from deficiency of the bifunctional enzyme AASS (605113) on chromosome 7q31. The AASS gene encodes lysine alpha-ketoglutarate reductase and saccharopine dehydrogenase, which catalyze, respectively, the sequential conversion of lysine to saccharopine and saccharopine to alpha-aminoadipic semialdehyde and glutamate (summary by Tondo et al., 2013). In hyperlysinemia type I, both enzymatic functions of AASS are defective and patients have increased serum lysine and possibly increased saccharopine; in hyperlysinemia type II, most of the first enzymatic function is retained, and patients tend to have isolated saccharopine increase (Cox, 1985; Cox et al., 1985).

Clinical Features

Carson et al. (1968) reported saccharopinuria in a 22-year-old moderately retarded, somewhat short girl with EEG abnormalities but no history of seizures; her urine also contained lysine, citrulline, and histidine. No other family members were affected.

Simell et al. (1972) described a 3.5-year-old girl with spastic diplegia who had lysinuria and saccharopinuria, but normal plasma levels of citrulline. Somatically and mentally she was normal. Simell et al. (1973) demonstrated deficiency of the saccharopine-degrading enzyme aminoadipic semialdehyde-glutamate reductase in cultured fibroblasts and in muscle. The enzyme was reduced to 40% of normal.

Cederbaum et al. (1979) reported a 7-year-old boy with mild developmental delay, hyperactivity, and speech delay who was found to have increased serum and urinary lysine and saccharopine. Saccharopine was also present in cerebrospinal fluid. Initial studies suggested cystinuria, but further analysis indicated that the amino acid was saccharopine. Patient fibroblasts showed undetectable activities of both lysine ketoglutarate reductase and saccharopine dehydrogenase. Reexamination of the urine of previously studied cases of this double enzyme deficiency (Dancis et al., 1976) suggested that saccharopinuria of variable degree is the rule and not the exception in patients with hyperlysinemia.