Inborn errors of the purine nucleotide cycle: Adenylosuccinase deficiency
Adenylosuccinase catalyses two reactions in purine metabolism: the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) into amino-imidazole carboxamide ribotide (AICAR) along the de novo synthesis of purine nucleotides, and the conversion of adenylosuccinate (S-AMP) into AMP in the conversion of IMP into AMP. The hallmarks of adenylosuccinase deficiency are the presence of succinylaminoimidazole carboxamide riboside (SAICAriboside) and succinyladenosine (S-Ado) in body fluids. These normally undetectable succinyl-purines are the products of the dephosphorylation, by cytosolic 5′-nucleotidase, of the two substrates of adenylosuccinase. The clinical picture of the enzyme deficiency is markedly heterogeneous with, as a rule, a profound, but nevertheless variable degree of psychomotor delay, often convulsions and/or autistic features, sometimes growth retardation and muscular dystrophy. The diagnostic tests that can be used for diagnosis, the enzyme and gene defects that have been identified, and the hypotheses that have been put forward to explain the pathophysiology of the disorder are reviewed.
- Aimi J, Badylak J, Williams J, Chen Z, Zalkin H, Dixon JE (1990) Cloning of a cDNA encoding adenylosuccinate lyase by functional complementation in Escherichia coli. J Biol Chem 265: 9011–9014.
- Barshop BA, Alberts AS, Gruber HE (1989) Kinetic studies of mutant human adenylosuccinase. Biochim Biophys Acta 999: 19–23.
- Bratton AC, Marshall AK (1939) A new coupling component for sulfanilamide determination. J Biol Chem 128: 537–550.
- De Bree PK, Wadman SK, Duran M, Fabery de Jonge H (1986) Diagnosis of inherited adenylosuccinase deficiency by thin-layer chromatography of urinary imidazoles and by automated cation exchange column chromatography of purines. Clin Chim Acta 156: 279–288.
- De Volder AG, Jaeken J, Van den Berghe G, et al (1988) Regional brain glucose utilization in adenylosuccinase-deficient patients measured by positron emission tomography. Pediatr Res 24: 238–242.
- Domkin VD, Lazebnik TA, Roudneff AY, Smirnov MN (1995) A new diagnostic technique for adenylosuccinate lyase deficiency. J Inher Metab Dis 18: 291–294.
- Dorland L, van Sprang FJ, van Echteld CJA, et al (1986) In vivo magnetic resonance spectroscopy and imaging of patients with adenylosuccinase deficiency. Annual Meeting of SSIEM, Amersfoort, The Netherlands, Abstract book P 150.
- Dunwiddie TV (1985) The physiological role of adenosine in the central nervous system. Int Rev Neurobiol 27: 63–139.
- Gross M, Gathof BS, Kölle P, Gresser U (1995) Capillary electrophoresis for screening of adenylosuccinate lyase deficiency. Electrophoresis 16: 1927–1929.
- Jaeken J, Van den Berghe G (1984) An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids. Lancet 2: 1048–1061.
- Jaeken J, Wadman SK, Duran M, et al (1988) Adenylosuccinase deficiency: an inborn error of purine nucleotide synthesis. Eur J Pediatr 148: 126–131.
- Jaeken J, Van den Bergh F, Vincent MF, Casaer P (1992) Adenylosuccinase deficiency: a newly recognized variant. J Inher Metab Dis 16: 416–418.
- Kmoch S, Hartmannova H, Krijt J, Sebesta I (1996) Adenylosuccinase deficiency — identification of a new disease causing mutation. J Inher Metab Dis 19(supplement 1): 13.
- Krijt J, Sebesta I, Svehlakova A, Zumrova A, Zeman J (1994) Adenylosuccinate lyase deficiency in a Czech girl and two siblings. Adv Exp Med Biol 370: 367–370.
- Laikind PK, Seegmiller JE, Gruber HE (1986a) Detection of 5′-phosphoribosyl-4-(N-succinylcarboxamide)-5-aminoimidazole in urine by use of the Bratton-Marshall reaction: identification of patients deficient in adenylosuccinate lyase activity. Anal Biochem 156: 81–90.
- Laikind PK, Gruber HE, Jansen I, et al (1986b) Purine biosynthesis in Chinese hamster cell mutants and human fibroblasts partially deficient in adenylosuccinate lyase. Adv Exp Med Biol 195B: 363–369.
- Lowenstein JM (1972) Ammonia production in muscle and other tissues: the purine nucleotide cycle. Physiol Rev 52: 384–414.
- Maaswinkel-Mooij PD, Laan LAEM, Onkenhout W, Poorthuis BJHM (1996) Epileptic seizures as presenting symptom in adenylosuccinase deficiency. J Inher Metab Dis 19(supplement 1): 12.
- Maddocks J, Reed T (1989) Urine test for adenylosuccinase deficiency in autistic children. Lancet 1: 158–159.
- Sabina RL, Patterson D, Holmes EW (1985) 5-Amino-4-imidazole-carboxamide riboside (Z-riboside) metabolism in eukaryotic cells. J Biol Chem 260: 6107–6114.
- Salerno C, Crifo C, Giardini O (1995) Adenylosuccinate lyase deficiency: a patient with impaired erythrocyte activity and anomalous response to intravenous fructose. J Inher Metab Dis 18: 602–608.
- Sebesta I, Krijt J, Kmoch S, Hartmannova H, Wojda M, Zeman J (1996) Adenylosuccinase deficiency — clinical and biochemical findings in 5 Czech patients. J Inher Metab Dis 19(supplement 1): 2.
- Sidi Y, Mitchell BS (1985) Z-Nucleotide accumulation in erythrocytes from Lesch-Nyhan patients. J Clin Invest 76: 2416–2419.
- Stone RL, Aimi J, Barshop BA, et al (1992) A mutation in adenylosuccinate lyase associated with mental retardation and autistic features. Nature Genet 1: 59–63.
- Stone RL, Zalkin H, Dixon JE (1993) Expression, purification and kinetic characterization of recombinant human adenylosuccinate lyase. J Biol Chem 268: 19710–19716.
- Valik D, Miner PT, Jones JD (1996) Clinical and biochemical findings in a first North American case of adenylosuccinase deficiency. J Inher Metab Dis 19(supplement 1): 11.
- Van den Bergh F, Vincent MF, Jaeken J, Van den Berghe G (1991) Radiochemical assay of adenylosuccinase: demonstration of parallel loss of activity toward both adenylosuccinate and succinylaminoimidazole carboxamide ribotide of patients with the enzyme defect. Anal Biochem 193: 287–291.
- Van den Bergh F, Vincent MF, Jaeken J, Van den Berghe G (1993a) Residual adenylosuccinase activities in fibroblasts of adenylosuccinase-deficient children: Parallel deficiency with adenylosuccinate and succinyl-AICAR in profoundly retarded patients and non-parallel deficiency in a mildly retarded girl. J Inher Metab Dis 16: 415–424.
- Van den Bergh F, Vincent MF, Jaeken J, Van den Berghe G (1993b) Functional studies in fibroblasts of adenylosuccinase-deficient children. J Inher Metab Dis 16: 425–434.
- Van den Berghe G, Jaeken J (1986) Adenylosuccinase deficiency. Adv Exp Med Biol 195A: 27–33.
- Van den Berghe G, Bontemps F, Vincent MF, Van den Bergh F (1992) The purine nucleotide cycle and its molecular defects. Progr Neurobiol 39: 547–561.
- Van Keuren ML, Hart IM, Kao FT, et al (1987) A somatic cell hybrid with a single human chromosome 22 corrects the defect in the CHO mutant (Ade-I) lacking adenylosuccinase activity. Cytogenet Cell Genet 44: 142–147.
- Vincent MF, Van den Berghe G (1989) Influence of succinylpurines on the binding of adenosine to a particular fraction of rat cerebral cortex. Adv Exp Med Biol 253B: 441–445.
- Vincent MF, Marangos PJ, Gruber HE, Van den Berghe G (1991) Inhibition by AICAriboside of gluconeogenesis in isolated rat hepatocytes. Diabetes 40: 1259–1266.
- Inborn errors of the purine nucleotide cycle: Adenylosuccinase deficiency
Journal of Inherited Metabolic Disease
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