THE MNGIE SYNDROME IN 2 SIBLINGS

Two siblings (one man, one woman), presenting with diarrhea, severe we ight loss, peripheral neuropathy, ophthalmoparesis, asymptomatic leuko encephalopathy were diagnosed as new cases of Mitochondrial Neuro Gast ro Intestinal Encephalomyopathy syndrom (MNGIE). Hirano (1994) defined four criteria for the diagnostic: peripheral neuropathy, ophthalmopar esis, gastro intestinal dysmotility, muscle biopsy with histologic fea tures of mitochondrial myopathy (ragged-red fibers, muscle fibers with increased succinate deshydrogenase stain or ultra-structurally abnorm al mitochondria). In a review of the literature, we found 31 cases wit h 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 extreme s from I 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 l oss in I case. During the evolution, besides the cardinal signs, the f ollowing features have been observed with a variable frequency: hearin g loss, short stature, facial palsy, dysphonia, dysarthria, dysphagia, sweating, orthostatic hypotension, bladder dysfunction, hepatomegalia . The laboratory features are. abnormal Nerve Conduction Studies/EMG c ompatible with a sensory motor neuropathy, lactic acidosis, mitochondr ial respiratory chain defect (essentially complex IV deficiency comple x I deficiency or multiple complex defect), MRI leukodystrophy, elevat ed CSF protein, heart block, ragged-red fibers or increased SDH stain. The prognosis is poor, due to a severe weight loss bordering on cache xia 13 patients died with a mean age of 28.5 years (median 24 years, e xtreme 3 years to 51 years). The prognosis seems to be worsened by a y oung 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 affe cted. The study of these families is compatible with an autosomic rece ssive transmission, suggesting a pathology of the nuclear genomi, prob ably impliying the control of the mitochondrial DNA replication. In fa ct, in 13 cases, a study of the mt DNA was realized: multiple deletion s were founded in 6 cases, multiples mutations in one case, unique mut ation in I case. In 5 cases there was no evidence of abnormality. The precise etiology and pathophysiologic significance of the mt DNA delet ions, and the heterogeneity of the modifications of the mt DNA remain unknown. However, the possibility of various phenotypes for a same gen otype or inversely is known in mitochondriopathies.