Lu Wang, Ying Xiong, Kaiyan Jiang, Dandan Tan, Liya Zhang, Min Zhu, Meihong Zhou, Yusen Qiu, Daojun Hong
{"title":"DLD基因的新型双等位变异引起可逆性感觉神经病变。","authors":"Lu Wang, Ying Xiong, Kaiyan Jiang, Dandan Tan, Liya Zhang, Min Zhu, Meihong Zhou, Yusen Qiu, Daojun Hong","doi":"10.1111/cge.70052","DOIUrl":null,"url":null,"abstract":"<p><p>Dihydrolipoamide dehydrogenase deficiency (DLDD) is a rare autosomal recessive disorder that typically affects the liver, brain, and muscle. Peripheral neuropathy has not been previously associated with this condition. We report a novel case of DLDD in a 20-year-old woman who presented with recurrent hepatic dysfunction and progressive sensory neuropathy. Clinical evaluation, electrophysiology, and nerve biopsy revealed a severe sensory axonal neuropathy with lipid accumulation. Genetic analysis identified compound heterozygous DLD variants (c.745G>T, p.G249C; c.1344_1347del, p.D448Efs*16), and Western blotting confirmed markedly reduced DLD protein in patient-derived fibroblasts. Treatment with a branched-chain amino acid (BCAA)-free formula, methylcobalamin, and thiamine led to complete resolution of vomiting and significant improvement in neuropathic symptoms, as confirmed by follow-up nerve conduction studies. This is the first report to link DLDD with a reversible sensory neuropathy, expanding the phenotypic spectrum of the disease. Our findings suggest a role for lipid dysregulation and metabolic imbalance in the pathogenesis of peripheral nerve involvement and support early targeted dietary therapy in patients with atypical DLDD presentations.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Novel Biallelic Variants in DLD Gene Cause a Reversible Sensory Neuropathy.\",\"authors\":\"Lu Wang, Ying Xiong, Kaiyan Jiang, Dandan Tan, Liya Zhang, Min Zhu, Meihong Zhou, Yusen Qiu, Daojun Hong\",\"doi\":\"10.1111/cge.70052\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Dihydrolipoamide dehydrogenase deficiency (DLDD) is a rare autosomal recessive disorder that typically affects the liver, brain, and muscle. Peripheral neuropathy has not been previously associated with this condition. We report a novel case of DLDD in a 20-year-old woman who presented with recurrent hepatic dysfunction and progressive sensory neuropathy. Clinical evaluation, electrophysiology, and nerve biopsy revealed a severe sensory axonal neuropathy with lipid accumulation. Genetic analysis identified compound heterozygous DLD variants (c.745G>T, p.G249C; c.1344_1347del, p.D448Efs*16), and Western blotting confirmed markedly reduced DLD protein in patient-derived fibroblasts. Treatment with a branched-chain amino acid (BCAA)-free formula, methylcobalamin, and thiamine led to complete resolution of vomiting and significant improvement in neuropathic symptoms, as confirmed by follow-up nerve conduction studies. This is the first report to link DLDD with a reversible sensory neuropathy, expanding the phenotypic spectrum of the disease. Our findings suggest a role for lipid dysregulation and metabolic imbalance in the pathogenesis of peripheral nerve involvement and support early targeted dietary therapy in patients with atypical DLDD presentations.</p>\",\"PeriodicalId\":10354,\"journal\":{\"name\":\"Clinical Genetics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Genetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/cge.70052\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cge.70052","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
摘要
二氢脂酰胺脱氢酶缺乏症(DLDD)是一种罕见的常染色体隐性遗传病,通常影响肝脏、大脑和肌肉。周围神经病变以前没有与这种情况相关。我们报告一个新的病例DLDD在一个20岁的妇女谁提出了复发性肝功能障碍和进行性感觉神经病变。临床评估,电生理和神经活检显示严重的感觉轴索神经病伴脂质积累。遗传分析鉴定出复合杂合DLD变异(c.745G b> T, p.G249C; c.1344_1347del, p.D448Efs*16), Western blotting证实患者源性成纤维细胞中DLD蛋白显著降低。随访神经传导研究证实,用无支链氨基酸(BCAA)配方、甲基钴胺素和硫胺素治疗可完全缓解呕吐,并显著改善神经性症状。这是第一个将DLDD与可逆性感觉神经病变联系起来的报告,扩大了该疾病的表型谱。我们的研究结果表明脂质失调和代谢失衡在周围神经受累的发病机制中起作用,并支持非典型DLDD患者早期靶向饮食治疗。
Novel Biallelic Variants in DLD Gene Cause a Reversible Sensory Neuropathy.
Dihydrolipoamide dehydrogenase deficiency (DLDD) is a rare autosomal recessive disorder that typically affects the liver, brain, and muscle. Peripheral neuropathy has not been previously associated with this condition. We report a novel case of DLDD in a 20-year-old woman who presented with recurrent hepatic dysfunction and progressive sensory neuropathy. Clinical evaluation, electrophysiology, and nerve biopsy revealed a severe sensory axonal neuropathy with lipid accumulation. Genetic analysis identified compound heterozygous DLD variants (c.745G>T, p.G249C; c.1344_1347del, p.D448Efs*16), and Western blotting confirmed markedly reduced DLD protein in patient-derived fibroblasts. Treatment with a branched-chain amino acid (BCAA)-free formula, methylcobalamin, and thiamine led to complete resolution of vomiting and significant improvement in neuropathic symptoms, as confirmed by follow-up nerve conduction studies. This is the first report to link DLDD with a reversible sensory neuropathy, expanding the phenotypic spectrum of the disease. Our findings suggest a role for lipid dysregulation and metabolic imbalance in the pathogenesis of peripheral nerve involvement and support early targeted dietary therapy in patients with atypical DLDD presentations.
期刊介绍:
Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice.
Topics of particular interest are:
• Linking genetic variations to disease
• Genome rearrangements and disease
• Epigenetics and disease
• The translation of genotype to phenotype
• Genetics of complex disease
• Management/intervention of genetic diseases
• Novel therapies for genetic diseases
• Developmental biology, as it relates to clinical genetics
• Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease