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

Molecular Genetics and Metabolism Reports

卷:23

Paola Sabrina Buonuomo¹  Andrea Bartuli²  Gerrit Weber²  Beatrice Testa²  Emanuele Bellacchio³  Francesco Cecconi⁴  Marco Tartaglia⁴  Gerarda Mastrogiorgio⁵  Marina Macchiaiolo⁵  Matteo Bordi⁵ 

[1] Corresponding author.;

[2] Department of Biology, University of Rome Tor Vergata, Rome, Italy;

[3] Department of Pediatric Hematology/Oncology, Bambino Gesù Children Hospital, IRCCS, Roma, Italy;

[4] Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy;

[5] Rare Diseases and Medical Genetics Unit, Academic Department of Pediatrics (DPUO), Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy;

关键词: Adenylosuccinate lyase deficiency;    Purine metabolism;    Exome sequencing;    Autophagy;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown