ADENYLOSUCCINASE DEFICIENCY: 217

Abstract

Adenylosuccinase (ASase) deficiency was suspected in 3 mentally retarded autistic children by the discovery of succinyl-adenosine (S-Ado) and SAICAriboside in their body fluids and confirmed in case A by the finding of an absence of enzyme activity in the kidney and of a partial deficiency in the liver (Jaeken & Van den Berghe, Lancet 2:1058, 1984). Further studies of ASase (nmol/min/mg protein vs means ± SEM in 5-8 controls) in cases B and C have shown a partial deficiency in kidney (0.18 and 0.21 vs 1.08 ± 0.10), liver (0.14 and 0.11 vs 0.72 ± 0.18) and muscle (0.18 and 0.66 vs 2.61 ± 0.34). In the lymphocytes and fibroblasts of the 3 cases, mean ASase activity was respectively 37 and 63 % of control. HPLC measurements of metabolites in quick-frozen kidney of cases A & B showed an accumulation of S-AMP (0.2 mM vs undetectable in controls) whereas no SAICAribotide could be found. In case A there was an approx. 4-fold increase of the adenine, guanine and uridine nucleotides; only the latter were similarly increased in case B.In quick-frozen liver of the 3 cases S-AMP was comparable to controls, no SAICAribotide could be detected but the concentration of an unknown compound, migrating just prior to the nucleotide 3-phosphates was decreased by approx. 50 %. ASase deficiency seems to induce a secondary increase of the synthesis of nucleotides by the PRPP transferases and/or a decrease of their degradation in the kidney and to hinder the formation of a derivative of the "de novo" pathway in the liver. Supported by FRSM, FWGO & CST 17645.