Very mild isolated intellectual disability caused by adenylosuccinate lyase deficiency: a new phenotype.

• 影响指数: 2.082
• 发表时间: Jun 2020
• 来源期刊: Mol Genet Metab Rep
• DOI: 10.1016/j.ymgmr.2020.100592
• PMID: 32405461
• 文章类型: Case Reports
• 作者列表: Macchiaiolo M,Buonuomo PS,Mastrogiorgio G,Bordi M,Testa B,Weber G,Bellacchio E,Tartaglia M,Cecconi F,Bartuli A

关键词: ADSL, Adenylosuccinate lyase deficiency; AICAr, Aminoimidazole carboxamide ribotide; AMP, Adenosine monophosphate; Adenylosuccinate lyase deficiency; Autophagy; Exome sequencing; MRI, magnetic resonance imaging; Purine metabolism; S- Ado, Succinyladenosine; S-AMP, Adenylosuccinate; SAICAR, succinyl-aminoimidazole carboxamide ribotide

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.