Macchiaiolo Marina, Buonuomo Paola Sabrina, Mastrogiorgio Gerarda, Bordi Matteo, Testa Beatrice, Weber Gerrit, Bellacchio Emanuele, Tartaglia Marco, Cecconi Francesco, Bartuli Andrea
Rare Diseases and Medical Genetics Unit, Academic Department of Pediatrics (DPUO), Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Mol Genet Metab Rep. 2020 May 6;23:100592. doi: 10.1016/j.ymgmr.2020.100592. eCollection 2020 Jun.
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 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.
腺苷酸琥珀酸裂解酶缺乏症是一种罕见的嘌呤代谢神经代谢隐性疾病，具有广泛的临床表现。我们报告了两名兄弟姐妹的非常轻微的表型，其特征为轻度孤立性认知障碍，无脑异常、癫痫发作、脑电图异常且疾病无进展。在进行临床外显子组检测之前，对这两名患者的检查均未成功。在两名兄弟姐妹中，均检测到基因中两个遗传错义变体的复合杂合性，即c.76A>T（p.Met26Leu）和c.1187G>A（p.Arg396His）。对来自男性患者的EBV转化的B淋巴母细胞样细胞的自噬分解代谢途径分析排除了基础水平存在任何自噬改变的情况。有必要进行进一步研究以了解该疾病的发病机制，并阐明自噬在腺苷酸琥珀酸裂解酶缺乏症发展中的潜在作用。
