The Clinical Aspects of ASase Deficiency

Abstract

The discovery of adenylosuccinate lyase (EC 4.3.22; adenylosuccinase; ASase) deficiency has been the result of a new approach to investigating children with unexplained psychomotor retardation, i.e., systematic amino acid analysis of the cerebrospinal fluid (CSF) before and after strong acid hydrolysis (Jaeken 1985). In three children with severe psychomotor retardation and autistic features this technique revealed a marked increase of aspartate and glycine in CSF, only after acid hydrolysis. As a consequence of this unexpected and intriguing finding a number of additional investigations were performed on CSF including thin-layer chromatography of mono- and disaccharides which resulted in another surprise: an increase of bound ribose. Since ribose, glycine, and aspartate are building blocks of the purine skeleton the de novo purine pathway emerged as the probable site of the basic defect, more specifically at its ASase step. This hypothesis was confirmed by finding in the CSF but also in the plasma and urine of these children an accumulation of succinyladenosine (S-Ado) and succinylaminoimidazole carboxamide (SAICA) ribose, the dephosphorylated derivatives of the two substrates of ASase and by demonstrating the enzymatic defect in a number of tissues (Jaeken and Van den Berghe 1984).