Abstract
Clinical and biochemical data are presented on eight children with adenylosuccinase deficiency. This newly discovered inborn error of purine metabolism is characterized by an accumulation in body fluids of succinyladenosine (S-Ado) and succinylaminoimidazole carboxamide riboside (SAICA riboside), the dephosphorylated derivatives of the two substrates of adenylosuccinase. Six living children (three boys and three girls) and one deceased sibling displayed severe psychomotor retardation. Epilepsy was documented in five cases, autistic features in three, and growth retardation associated with muscular wasting in a brother and sister. In the cerebrospinal fluid, plasma and urine of these patients, the S-Ado/SAICA riboside ratio was between 1 and 2. In striking contrast, the eighth patient (a girl) was markedly less mentally retarded. Most noteworthy, the S-Ado/SAICA riboside ratio in her body fluids was around 5, suggesting that her milder psychomotor retardation was causally linked to this higher ratio. Adenylosuccinase deficiency was demonstrated in the liver of all seven living children, in the kidney of three patients in whom the enzymatic activity was measured, and in the muscle of three patients, including the two with muscular wasting. In fibroblasts of the six severely retarded patients, adenylosuccinase activity was reduced to approximately 40% of normal; in the patient with the higher S-Ado/SAICA riboside ratio, it reached only 6% of normal. The clinical heterogeneity of adenylosuccinase deficiency justifies systematic screening for the enzyme defect in unexplained neurological disease.
Similar content being viewed by others
Abbreviations
- AICAR:
-
aminoimidazole carboxamide ribotide
- AMP:
-
adenosine monophosphate
- APRT:
-
adenine phosphoribosyl transferase
- HGPRT:
-
hypoxanthine-guanine phosphoribosyl transferase
- IMP:
-
inosine monophosphate
- PRPP:
-
phosphoribosyl pyrophosphate
- S-Ado:
-
succinyladenosine
- SAICA:
-
succinylaminoimidazole carboxamide
- SAICAR:
-
succinylaminoimidazole carboxamide ribotide
- S-AMP:
-
adenylosuccinate (succinyl AMP)
- ZTP:
-
AICAR triphosphate
References
Adams RD, Lyon G (1982) Neurology of hereditary metabolic diseases of children. McGraw-Hill, New York
American Psychiatric Association (1980) DSM-III: diagnostic and statistical manual of mental disorders, 3rd edn. A.P.A., Washington, DC
Brand LM, Lowenstein JM (1978) Effect of diet on adenylosuccinase activity in various organs of rat and chicken. J Biol Chem 253:6872–6878
Bratton AC, Marshall EK (1939) A new coupling component for sulfanilamide determination. J Biol Chem 128:537–550
Bree PK de, Wadman SK, Duran M, Fabery de Jonge H (1986) Diagnosis of inherited adenylosuccinase deficiciency by thin-layer chromatography of urinary imidazoles and by automated cation exchange column chromatography of purines. Clin Chim Acta 156:279–288
DeMyer W, DeMyer M (1984) Infantile autism. Neurol Clin 2: 139–152
Dorland L, Sprang FJ van, Echteld CJA van, Duran M, Wadman SK, Hollander JA den, Luyten PR (1986) In vivo magnetic resonance spectroscopy and imaging of patients with adenylosuccinase deficiency. Annual Meeting of the SSIEM, abstract book P150. Amersfoort, The Netherlands
Fox IH, Kelley WN (1978) The role of adenosine and 2′-deoxyadenosine in mammalian cells. Annu Rev Biochem 47:655–686
Fredholm BB, Hedqvist P (1980) Modulation of neurotransmission by purine nucleotides and nucleosides. Biochem Pharmacol 29:1635–1643
Jaeken J, Van den Berghe G (1984) An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids. Lancet II:1058–1061
Kaufman JM, Greene ML, Seegmiller JE (1968) Urine uric acid to creatinine ratio — a screening test for inherited disorders of purine metabolism. J Pediatr 73:583–592
Kelley WN, Wyngaarden JB (1983) Clinical syndromes associated with hypoxanthine-guanine phosphoribosyl transferase deficiency. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease. Mc Graw-Hill, New York, pp 1115–1143
Laikind PK, Seegmiller JE, Gruber HE (1986) 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
Lowenstein JM (1972) Ammonia production in muscle and other tissues: the purine nucleotide cycle. Physiol Rev 52:382–414
Marangos PJ, Boulenger JP (1985) Basic and clinical aspects of adenosinergic neuromodulation. Neurosci Biobehav Rev 9:421–430
Schultz V, Lowenstein JM (1976) Purine nucleotide cycle. Evidence for the occurrence of the cycle in brain. J Biol Chem 251: 485–492
Sidi Y, Mitchell BS (1985) Z-nucleotide accumulation in erythrocytes from Lesch-Nyhan patients. J Clin Invest 76:2416–2419
Van den Berghe G, Jaeken J (1986) Adenylosuccinase deficiency. Adv Exp Med Biol 195A:27–33
Van den Berghe G, Jaeken J (1986) Use of the Bratton-Marshall test for the diagnosis of adenylosuccinase deficiency (in Dutch). Versl Belg Ver Kindergen 18:42–46
Wadman SK, Bree PK de, Duran M, Fabery de Jonge H (1986) Detection of inherited adenylosuccinase deficiency by two dimensional thin layer chromatography of urinary imidazoles. Adv Exp Med Biol 195A:21–25
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jaeken, J., Wadman, S.K., Duran, M. et al. Adenylosuccinase deficiency: an inborn error of purine nucleotide synthesis. Eur J Pediatr 148, 126–131 (1988). https://doi.org/10.1007/BF00445919
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00445919