Prasun Pankaj, Young Sarah, Salomons Gajja, Werneke Andrea, Jiang Yong-Hui, Struys Eduard, Paige Mikell, Avantaggiati Maria Laura, McDonald Marie
Divison of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, 27710, USA.
JIMD Rep. 2015;19:111-5. doi: 10.1007/8904_2014_378. Epub 2015 Jan 23.
Recessive mutations in SLC25A1 encoding mitochondrial citrate carrier cause a rare inherited metabolic disorder, combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA), characterized by epileptic encephalopathy, respiratory insufficiency, developmental arrest and early death. Here, we describe two siblings compound heterozygotes for null/missense SLC25A1 mutations, c.18_24dup (p.Ala9Profs*82), and c.134C>T (p.Pro45Leu). These children presented with classic clinical features of D,L-2-HGA, but also showed marked facial dysmorphism. Additionally, there was prominent lactic acidosis in one of the siblings. Our observations suggest that facial dysmorphism is a previously unrecognized but an important diagnostic feature of SLC25A1 deficiency and expand the clinical phenotype linked to SLC25A1 mutations.
编码线粒体柠檬酸载体的SLC25A1基因发生隐性突变会导致一种罕见的遗传性代谢紊乱疾病，即合并型D，L-2-羟基戊二酸尿症（D，L-2-HGA），其特征为癫痫性脑病、呼吸功能不全、发育停滞及早期死亡。在此，我们描述了两名SLC25A1基因存在无效/错义突变（c.18_24dup，p.Ala9Profs*82和c.134C>T，p.Pro45Leu）的复合杂合子同胞。这些患儿具有D，L-2-HGA的典型临床特征，但也表现出明显的面部畸形。此外，其中一名同胞还存在显著的乳酸性酸中毒。我们的观察结果表明，面部畸形是SLC25A1缺乏症此前未被认识到但重要的诊断特征，并扩展了与SLC25A1突变相关的临床表型。
