Department of Neurology, National Institute of Mental health and Neurosciences, Bangalore, India.
J Neurol Sci. 2011 Oct 15;309(1-2):131-5. doi: 10.1016/j.jns.2011.06.052. Epub 2011 Jul 26.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a distinctive autosomal recessive disorder with mitochondrial alterations due to mutations TYMP gene encoding thymidine phosphorylase.
Study of clinical and biochemical characteristics of a family with MNGIE.
Index case was a 32 year old man presenting with recurrent vomiting, early satiety and progressive weight loss. He had ptosis, restricted eye movements, generalized muscle wasting, and absent tendon reflexes. Lactate levels were elevated in venous blood and CSF lactate. MRI brain showed diffuse leucoencephalopathy. Barium swallow showed near total obstruction at mid portion of vertical limb of duodenum with ileus. Esophageal manometry suggested myopathy. Muscle biopsy revealed moderate numbers of ragged blue and ragged red fibers as well as cytochrome c oxidase deficient fibers. An elder brother had similar symptoms and expired after a surgical procedure and a 28 year old brother has similar illness. The father had asymptomatic bilateral ptosis with mild ophthalmoparesis. The paternal grandfather and paternal aunt also had bilateral ptosis. Clinical diagnosis of MNGIE was confirmed in the two living brothers by demonstrating severe defects of thymidine phosphorylase activity in buffy coat, elevated thymidine and deoxyuridine in plasma, and a homozygous TYMP c.893G>A mutation.
This family with biochemically and genetically confirmed mitochondrial neurogastrointestinal encephalopathy syndrome uncharacteristically included heterozygous TYMP mutation carriers manifesting extra-ocular weakness. It is important to identify MNGIE patients early because therapeutic options are emerging.
线粒体神经胃肠脑肌病（MNGIE）是一种独特的常染色体隐性疾病，由于编码胸苷磷酸化酶的 TYMP 基因突变导致线粒体改变。
研究一个 MNGIE 家族的临床和生化特征。
索引病例是一名 32 岁男性，表现为反复呕吐、早饱和进行性体重减轻。他有眼睑下垂、眼球运动受限、全身肌肉消瘦和腱反射消失。静脉血和 CSF 乳酸水平升高。脑部 MRI 显示弥漫性脑白质病变。钡餐显示十二指肠垂直肢中部几乎完全梗阻伴肠梗阻。食管测压提示肌病。肌肉活检显示中度数量的杂乱蓝纤维和杂乱红纤维以及细胞色素 c 氧化酶缺陷纤维。一位哥哥有类似的症状，在手术后去世，一位 28 岁的哥哥也有类似的疾病。父亲有双侧无症状眼睑下垂伴轻度眼肌麻痹。祖父和姑妈也有双侧眼睑下垂。通过在两个幸存的兄弟的白细胞中检测到胸苷磷酸化酶活性严重缺陷、血浆中胸苷和脱氧尿苷升高以及 TYMP c.893G>A 突变的纯合子，确认了这两个兄弟的 MNGIE 临床诊断。
这个具有生化和遗传确认的线粒体神经胃肠脑肌病综合征家族非同寻常地包括表现出眼外肌无力的杂合 TYMP 突变携带者。早期识别 MNGIE 患者非常重要，因为治疗选择正在出现。
