Debouverie M, Wagner M, Ducrocq X, Grignon Y, Mousson B, Weber M
Service de Neurologie, CHU Nancy.
Rev Neurol (Paris). 1997 Oct;153(10):547-53.
Two siblings (one man, one woman), presenting with diarrhea, severe weight loss peripheral neuropathy, ophthalmoparesis, asymptomatic leukoencephalopathy were diagnosed as a new cases of Mitochondrial Neuro Gastro Intestinal Encephalomyopathy syndrome (MNGIE). Hirano (1994) defined four criteria for the diagnostic: peripheral neuropathy, ophthalmoparesis, gastro intestinal dysmotility, muscle biopsy with histologic features of mitochondrial myopathy (ragged-red fibers, muscle fibers with increased succinate deshydrogenase stain or ultra structurally abnormal mitochondria). In a review of the literature, we found 31 cases with MNGIE. With our two cases, we study this group of 33 patients. First symptoms begin about 13.5 years with a median of 10 years and extremes for 1 to 32 years. The first signs are gastro intestinal symptoms (recurrent nausea, vomiting or diarrhea with intestinal dysmotility) in 22 cases, an ophthalmoparesia in 4 cases, intestinal and ocular signs in 1 case, gait ataxia or peripheral neuropathy in 3 cases, hearing loss in 1 case, gait ataxia or peripheral neuropathy in 3 cases, hearing loss in 1 case. During the evolution, besides the cardinal signs, the following features have been observed with a variable frequency: hearing loss, short stature, facial palsy, dysphonia, dysarthria, sweating, orthostatic hypotension, bladder dysfunction, hepatomegalia, The laboratory features are: abnormal Nerve Condition Studies/EMG compatible with a sensory motor neuropathy, lactic acidosis, mitochondrial respiratory chain defect (essentially complex IV deficiency, complex I deficiency or multiple complex defect), MRI leukodystrophy, elevated CSF protein, heart block, ragged-red fibers or increased SDH stain. The prognosis is poor, due to a severe weight loss bordering on cachexia 13 patients died with a mean age of 28.5 years (median 24 years, extreme 3 years to 51 years). The prognosis seems to be worsened by a young age of onset. The 33 patients belong to 19 families with 7 cases of consanguinity. 25 patients had a brother, a sister or a cousin affected. The study of these families is compatible with an autosomic recessive transmission, suggesting a pathology of the nuclear genomi, probably impliying the control of the mitochondrial DNA replication. In fact, in 13 cases, a study of the mt DNA was realized: multiple deletions were founded in 6 cases, multiples mutations in one case, unique mutation in 1 case. In 5 cases ther was no evidence of abnormality. These precise etiology and pathophysiologic significance of the mt DNA deletions, and the heterogeneity of the modifications of the mt DNA remain unknown. However, the possibility of various phenotypes for a same genotype or inversely is known in mitochondriopathies.
两名兄弟姐妹（一男一女），出现腹泻、严重体重减轻、周围神经病变、眼肌麻痹、无症状性白质脑病，被诊断为线粒体神经胃肠脑肌病综合征（MNGIE）的新病例。Hirano（1994年）定义了四项诊断标准：周围神经病变、眼肌麻痹、胃肠动力障碍、肌肉活检具有线粒体肌病的组织学特征（破碎红纤维、琥珀酸脱氢酶染色增加的肌纤维或超微结构异常的线粒体）。在文献综述中，我们发现31例MNGIE病例。加上我们的两例病例，我们对这33例患者进行了研究。首发症状开始于约13.5岁，中位数为10岁，范围为1至32岁。首发体征在22例中为胃肠症状（反复恶心、呕吐或腹泻伴肠道动力障碍），4例为眼肌麻痹，1例为肠道和眼部体征，3例为步态共济失调或周围神经病变，1例为听力丧失，3例为步态共济失调或周围神经病变，1例为听力丧失。在疾病进展过程中，除了主要体征外，还观察到以下不同频率出现的特征：听力丧失、身材矮小、面神经麻痹、发音困难、构音障碍、出汗、体位性低血压、膀胱功能障碍、肝肿大。实验室特征为：神经电生理检查/肌电图异常，符合感觉运动神经病变，乳酸酸中毒，线粒体呼吸链缺陷（主要为复合体IV缺乏、复合体I缺乏或多种复合体缺陷），MRI显示白质营养不良，脑脊液蛋白升高，心脏传导阻滞，破碎红纤维或琥珀酸脱氢酶染色增加。预后较差，由于严重体重减轻接近恶病质，13例患者死亡，平均年龄28.5岁（中位数24岁，范围3至51岁）。发病年龄较轻似乎使预后更差。这33例患者属于19个家庭，其中7例有近亲关系。25例患者有兄弟、姐妹或表亲患病。对这些家庭的研究符合常染色体隐性遗传，提示核基因组病变，可能涉及线粒体DNA复制的控制。事实上，在13例病例中进行了线粒体DNA研究：6例发现多个缺失，1例发现多个突变，1例发现单个突变。5例未发现异常证据。线粒体DNA缺失的确切病因和病理生理意义以及线粒体DNA修饰的异质性仍然未知。然而，在线粒体病中，同一基因型可能有多种表型或反之亦然的情况是已知的。
