Saccharopinuria: a New Inborn Error of Lysine Metabolism

Carson, Nina A. J.; Scally, B.G.; Neill, D. W.; Carré, I. J.

doi:10.1038/218679a0

Cited by 80 publications

(33 citation statements)

References 9 publications

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“…This seems unlikely in our patients since serum lysine response to a load is normal and blood lysine is low, not high. There appears to be no single set of circumstances that would explain these observations, either the striking citrullinemia in saccharopinuria (3), and the lysinuria of familial protein intolerance (12). There is no common cofactor requirement for these reactions.…”

Section: Discussionmentioning

confidence: 85%

Hyperornithinemia, Hyperammonemia, and Homocitrullinuria Associated with Decreased Carbamyl Phosphate Synthetase I Activity

et al. 1975

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Pediat. R e s . 9: 488--497 (1975) Extract Six related subjects with severe feeding problems in infancy, hyperammonemia, hyperornithinenia, and homocitrullinuria are reported. The clinical picture includes episodic motor and mental impairment, seizures, intellectual deficits that vary from severe to very mild and, in two cases, a bleeding tendency early in life. The pedigree indicates autosomal recessive inheritance.C a r b a m y l p h o s p h a t e synthetase I hyperornithinemia hoinocitrulliriuria leukocytes h y p e r a m m o n e m i aIn a liver biopsy in one patient decreased activity of carbamyl phosphate synthetase I ( C P S I, EC. 2.7.2.5) was found. Enzymatic assays on peripheral leukocytes in all six subjects confirmed the liver results. Loading studies with ornithine and citrulline were consistent with a defect early in the urea cycle. Homocitrullinuria appeared to arise from excessive synthesis from lysine, but there was no impairment of the main lysine catabolic pathway.Large and bizarrely shaped hepatic mitochondria with curious periodic (35@400W) membranes were observed ultrastructurally. SpeculationClinical entities in which liver C P S I deficiency has been reported represent a heterogeneous group. This heterogeneity may arise because the assays currently in use do not differentiate between individual steps in the complex synthetic reaction catalyzed by this enzyme. Associated abnormalities in ornithine transport into the hepatic mitochondria in some may also contribute to the varying expression of this group of disorders. It is conceivable that some unusual periodic structures observed just inside the inner mitochondrial membranes are related to altered ornithine mitochondria1 entry.This disorder adds to the evidence from other inborn errors that there are one or more ways in which lysine metabolism and the urea cycle are specifically interrelated, but the details remain obscure.In 1969 Shih et al. (23) described a patient with hyperammonemia who could be differentiated from the growing group of specific inherited hyperammonemias by the presence of markedly elevated blood ornithine and urinary homocitrulline in addition to the high levels of blood ammonia. Wright and Pollitt (28) reported briefly a second patient with these features.During the past several years we have had the opportunity to study six related subjects with this disorder, and carry out assays of the urea cycle enzymes on peripheral leukocytes of all, and on liver biopsy in one of these. In addition, ultrastructural examination was carried out on the biopsied hepatic tissue.It is the purpose of this communication to report on the results of the above study with special reference to clinical manifestations, localization of the metabolic block, possible mechanism of produc-48 tion of homocitrullinuria, and correlation of the biochemical and morphologic data. CLINICAL SUMMARIES CASE IThis severely mentally retarded boy, Figure 1 IV-8, first came to our attention at the age of 7 years when increased excretion of ornithine and lysi...

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Section: Discussionmentioning

confidence: 85%

Hyperornithinemia, Hyperammonemia, and Homocitrullinuria Associated with Decreased Carbamyl Phosphate Synthetase I Activity

et al. 1975

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“…The pipecolic pathway of lysine degradation to alpha-aminoadipic acid [7] is of secondary importance in humans but may be enhanced by substrate accumulation in lysine-ketoglutarate-reduct~e deficiency and in premature infants [8--10]. Hyperlysinaemia caused by a defective lysine ketoglutarate reductase [ 11- -13] and saccharopinuria [14,15] have been desclibed as alsturbances of the main lysine pathway. Two defects of the pipecolic acid pathway are known.…”

Section: Introductionmentioning

confidence: 99%

Alpha-ketoadipic aciduria, a new inborn error of lysine metabolism; biochemical studies

Przyrembel¹,

Bachmann²,

Lombeck³

et al. 1975

Clinica Chimica Acta

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SummaryInvestigation of a psychomotodcally retardcd girl showed excretion of abnormal amounts of alpha-ketoadipic acid, alpha-hydroxyadipic acid, alphaaminoadipic acid, 1,2-butenedicarboxylic acid and elevation of plasma alphaaminoadipic acid levels. T}-e identity of these metabolites was established by various methods. The excretion oi alpha-aminoadipic acid correlated to the lysine intake. Degradation studies with cultured fibroblasts indicate a defect in the oxidative decarboxyla:ion of alpha-ketoadipic acid (see Clin. Chim. Acta, 58 (1975) 271).

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“…A deficiency of the saccliaropine degrading enzyme was found in the Finnish patient [23]. T h e present paper reports the study of the enzymes involved in saccharopine metabolism in the original patient with saccllaropinuria [4] and in healthy control subjects utilizing skin fibroblast cultures and radioisotope techniques.…”

Section: Introducliorimentioning

confidence: 99%

Enzyme Studies in a Patient with Saccharopinuria: A Defect of Lysine Metabolism

Fellows

Carson

1974

Pediatr Res

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ExtractElevated levels of saccharopine, lysine, and citrulline in urine and plasma were observed in a patient suffering from saccharopinuria. Using radioisotope methods the lysine-degradative enzymes, lysine-oxoglutarate reductase and saccharopine dehyrogenase, were studied in skin fibroblasts grown from this patient and from healthy subjects.The results show that, in contrast to healthy individuals (range 177-320 pmol formed/min/mg protein), the paitent's fibroblasts are completely lacking in saccharopine dehydrogenase activity, which accounts for the presence of the high levels of saccharopine. The patient also has a reduced level of lysine-oxoglutarate reductase activity (333 pmol saccharopine formed/min/mg protein; range 550-1,570 nmol), which may in part explain the hyperlysinemia. A further enzyme saccharopine oxidoreductase which metabolizes saccharopine to lysine was found to be present in the patient's fibroblasts (63 pmol lysine formed/min/mg protein) but absent from those of healthy control subjects. This indicated induction of this enzyme by the patient in an attempt to reduce the high levels of saccharopine in her tissues and body fluid.

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Saccharopinuria: a New Inborn Error of Lysine Metabolism

Cited by 80 publications

References 9 publications

Hyperornithinemia, Hyperammonemia, and Homocitrullinuria Associated with Decreased Carbamyl Phosphate Synthetase I Activity

Hyperornithinemia, Hyperammonemia, and Homocitrullinuria Associated with Decreased Carbamyl Phosphate Synthetase I Activity

Alpha-ketoadipic aciduria, a new inborn error of lysine metabolism; biochemical studies

Enzyme Studies in a Patient with Saccharopinuria: A Defect of Lysine Metabolism

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