Hellebrekers Debby M E I, Sallevelt Suzanne C E H, Theunissen Tom E J, Hendrickx Alexandra T M, Gottschalk Ralph W, Hoeijmakers Janneke G J, Habets Daphna D, Bierau Jörgen, Schoonderwoerd Kees G, Smeets Hubert J M
Department of Clinical Genetics, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.
Department of Genetics and Cell Biology, School for Oncology and Developmental Biology, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.
Eur J Hum Genet. 2017 Jun;25(7):886-888. doi: 10.1038/ejhg.2017.62. Epub 2017 Apr 26.
In a 51-year-old patient of consanguineous parents with a severe neuromuscular phenotype of early-onset ataxia, myoclonia, dysarthria, muscle weakness and exercise intolerance, exome sequencing revealed a novel homozygous variant (c.-264_31delinsCTCACAAATGCTCA) in the mitochondrial FAD-transporter gene SLC25A32. Flavin adenine dinucleotide (FAD) is an essential co-factor for many mitochondrial enzymes and impaired mitochondrial FAD-transport was supported by a reduced oxidative phosphorylation complex II activity in the patient's muscle, decreased ATP production in fibroblasts, and a deficiency of mitochondrial FAD-dependent enzymes. Clinically, the patient showed improvement upon riboflavin treatment, which is a precursor of FAD. Our results confirm the recently reported case of SLC25A32 as a cause of riboflavin-responsive disease. Our patient showed a more severe clinical phenotype compared with the reported patient, corresponding with the (most likely) complete absence of the SLC25A32-encoding MFT (Mitochondrial Folate Transporter) protein.
在一名父母近亲结婚的51岁患者中，其患有早发性共济失调、肌阵挛、构音障碍、肌肉无力和运动不耐受的严重神经肌肉表型，外显子组测序显示线粒体FAD转运蛋白基因SLC25A32存在一种新的纯合变异（c.-264_31delinsCTCACAAATGCTCA）。黄素腺嘌呤二核苷酸（FAD）是许多线粒体酶的必需辅助因子，患者肌肉中氧化磷酸化复合体II活性降低、成纤维细胞中ATP生成减少以及线粒体FAD依赖性酶缺乏均支持线粒体FAD转运受损。临床上，该患者在接受作为FAD前体的核黄素治疗后症状有所改善。我们的结果证实了最近报道的SLC25A32作为核黄素反应性疾病病因的病例。与报道的患者相比，我们的患者表现出更严重的临床表型，这与（很可能）完全缺乏编码SLC25A32的MFT（线粒体叶酸转运蛋白）蛋白相符。
