Abstract
Adenylosuccinate lyase deficiency is a rare neurometabolic recessive disorder of purine metabolism characterized by a wide range of clinical manifestations. We present a very mild phenotype of two siblings characterized by mild isolated cognitive disability, in absence of brain anomalies, seizures, EEG anomalies and without progression of disease. The two patients had unsuccessfully been investigated until clinical exome was performed. In both siblings, compound heterozygosity for two inherited missense variants in ADSL gene, c.76A>T (p.Met26Leu) and c.1187G>A (p.Arg396His), were detected. Analysis of the catabolic pathway of autophagy on EBV-transformed B lymphoblastoid cell derived from the male patient excluded the presence of any autophagy alterations at the basal level. Further studies are necessary to understand the pathogenesis of the disease and to elucidate the potential role of autophagy in the development of ADSL deficiency.