Istituto di bioimmagini e fisiologia molecolare CNR-LATO, Cefalù PA, Scilly, Italy.
U.O. Neurologia, Fondazione Istituto "San Raffaele-G. Giglio", Cefalù PA, Scilly, Italy.
Nutrition. 2014 Apr;30(4):485-8. doi: 10.1016/j.nut.2013.10.008. Epub 2013 Oct 19.
Thiamine or vitamin B1 deficiency diminishes thiamine-dependent enzymatic activity, alters mitochondrial function, impairs oxidative metabolism, and causes selective neuronal death. We analyzed for the first time, the role of all known mutations within three specific thiamine carrier genes, SLC19 A2, SLC19 A3, and SLC25 A19, in a patient with atrophic beriberi, a multiorgan nutritional disease caused by thiamine deficiency.
A 44-year-old male alcoholic patient from Morocco developed massive bilateral leg edema, a subacute sensorimotor neuropathy, and incontinence. Despite normal vitamin B1 serum levels, his clinical picture was rapidly reverted by high-dose intramuscular thiamine treatment, suggesting a possible genetic resistance. We used polymerase chain reaction followed by amplicon sequencing to study all the known thiamine-related gene mutations identified within the Human Gene Mutation Database.
Thirty-seven mutations were tested: 29 in SLC19 A2, 6 in SLC19 A3, and 2 in SLC25 A19. Mutational analyses showed a wild-type genotype for all sequences investigated.
This is the first genetic study in beriberi disease. We did not detect any known mutation in any of the three genes in a sporadic dry beriberi patient. We cannot exclude a role for other known or unknown mutations, in the same genes or in other thiamine-associated genes, in the occurrence of this nutritional neuropathy.
硫胺素或维生素 B1 缺乏会降低依赖硫胺素的酶活性，改变线粒体功能，损害氧化代谢，并导致选择性神经元死亡。我们首次分析了三个特定硫胺素载体基因 SLC19A2、SLC19A3 和 SLC25A19 内所有已知突变在萎缩脚气病患者中的作用，萎缩脚气病是一种由硫胺素缺乏引起的多器官营养性疾病。
一位来自摩洛哥的 44 岁男性酒精中毒患者出现双侧腿部严重水肿、亚急性感觉运动神经病和失禁。尽管血清维生素 B1 水平正常，但大剂量肌内注射硫胺素治疗迅速逆转了他的临床症状，这表明可能存在遗传抗性。我们使用聚合酶链反应（PCR）后扩增子测序技术研究了在人类基因突变数据库中确定的所有已知与硫胺素相关的基因突变。
测试了 37 种突变：29 种在 SLC19A2 中，6 种在 SLC19A3 中，2 种在 SLC25A19 中。突变分析显示所有检测序列均为野生型基因型。
这是脚气病的第一项遗传研究。我们在一名散发性干性脚气病患者的三个基因中均未发现任何已知突变。我们不能排除其他已知或未知突变在同一基因或其他与硫胺素相关基因中导致这种营养性神经病的发生。
