Familal mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome in three siblings of consanguineous parents

Introduction: The mitochondria! neurogastrointestinal encephalomyopathy (MNGIE) is a rare disorder with simultaneous damage of the nuclear DNA (ncDNA) and mitochondria! DNA (mtDNA). It is clinically characterized by progressive ophthalmoplegia, peripheral neuropathy, leukoencephalopathy, gastrointestinal damage and premature death. Seven families with the MNGIE syndrome have been reported with thirty two patients affected either siblings or first cousins. Consanguinity has been reported once in the previous medical literature in two affected families. Patients and methods: We describe the clinical characteristics of a family with three sisters affected. One male brother did not have the disease. The siblings had consanguineous parents (first cousins). We made a search in Medline and PubMed up to September 2009 under the title of "Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and "oculogastrointestinal muscular dystrophy"(OGIMD). Results: We describe the clinical findings, the features of the MRI of the brain, the nerve conduction velocities and muscle biopsies of two of the affected siblings. The eldest sister died prematurely at age twenty three. The disease began in late childhood with gastrointestinal disorders; progressive deterioration of their nutritional state, ophthalmoplegia, fatigue and proximal muscle weakness. The brain MRI showed severe leukoencephalopathy, the nerve conduction velocities were slow and the muscle biopsy demonstrated ragged red fibers, The clinical findings, course of the disease and laboratory findings were characteristic of MNGIE. Conclusions: There are seven reports of familial MNGIE and one isolated report of consanguinity in two different families. In the family described in this article one male sibling did not have the disease. This is suggestive of autosomic dominant or recessive form of inheritance and is against transmission of a mutated mitochondrial DNA by the mother, We did not find a family history of the disease in four previous generations. This report also shows that the mutation of the ncDNA can condition very important changes in the mtDNA, which seem to be the direct cause of the symptoms, and illustrates the complex relations between the two types of DNA.