A New Case of Hyperlysinaemia with Saccharopinuria

Abstract

The main pathway for lysine catabolism in mammalian tissues proceeds through oxidative degradation forming saccharopine as a stable intermediate. The initial reaction is catalysed by lysine α-ketoglutarate reductase and the second by saccharopine dehydrogenase. It has been demonstrated (Marcovitz et al., 1984) on bovine liver that a single protein catalyses both reactions; this bifunctional enzyme has been called α-aminoadipic semialdehyde synthase by these authors. The second catabolic pathway for lysine, via pipecolic acid, although significant in some tissues (such as the central nervous system) is of less physiological importance. Familial hyperlysinaemia (McKusick 23870) was described for the first time in 1964. Until now, 13 patients in 9 families have been reported. Studies on skin fibroblasts identified the defective enzyme as lysine α-ketoglutarate reductase — but further studies in 7 of these patients revealed that saccharopine dehydrogenase activity was reduced to a similar extent (Dancis et al., 1979). Moreover, three other patients have been described who excreted excessive amounts of saccharopine as well as lysine (Carson et al., 1968; Simell et al., 1972, 1973; Cederbaum et al., 1979) and who have been reported as having saccharopinuria (McKusick 26870). The patient of Carson and colleagues exhibited a reduced activity of saccharopine dehydrogenase while lysine α-ketoglutarate reductase was only partially deficient (Fellows and Carson, 1974). Conversely, the patient of Cederbaum and colleagues (1979) had a multiple enzyme defect. Clinically, the three patients are slightly to deeply mentally retarded, with mild ataxia or small stature. We report here a new patient with hyperlysinaemia and hyperlysinuria in association with saccharopinuria.KeywordsAdipic AcidAmino Acid ProfileGlutaric AcidEnzyme DefectPipecolic AcidThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.