Familial mitochondrial intestinal pseudo-obstruction and neurogenic bladder

Intestinal dysmotility and neurogenic bladder have been described as part o f two autosomal-recessive mitochondrial disorders assumed to be due to a de fect in communication between the nuclear and mitochondrial genomes: myoneu rogastrointestinal encephalopathy (MNGIE) and diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (Wolfram syndrome). Partial cytochrom e c oxidase deficiency has been described in both. We describe three Ashken azi Jewish siblings with progressive intestinal dysmotility, neurogenic bla dder, and autonomic manifestations but no central nervous system involvemen t. Cytochrome c oxidase deficiency was demonstrated in peripheral and multi ple intestinal muscle biopsies. Mitochondrial DNA analysis of an intestinal biopsy of patient 1 showed heteroplasmy consisting of a normal 16.5-kb ban d and an approximately 28-kb band, suggestive of a duplication. Mitochondri al DNA analysis of a muscle biopsy of patient 2 showed multiple deletions, mainly 10- and Il-kb bands. We suggest that this unique combination of inte stinal pseudo-obstruction and neurogenic bladder could comprise a new autos omal-recessive mitochondrial disorder.