Familial mitochondrial intestinal pseudo-obstruction and neurogenic bladder.
Intestinal dysmotility and neurogenic bladder have been described as part of two autosomal-recessive mitochondrial disorders assumed to be due to a defect in communication between the nuclear and mitochondrial genomes: myoneurogastrointestinal encephalopathy (MNGIE) and diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (Wolfram syndrome). Partial cytochrome c oxidase deficiency has been described in both. We describe three Ashkenazi Jewish siblings with progressive intestinal dysmotility, neurogenic bladder, and autonomic manifestations but no central nervous system involvement. Cytochrome c oxidase deficiency was demonstrated in peripheral and multiple intestinal muscle biopsies. Mitochondrial DNA analysis of an intestinal biopsy of patient 1 showed heteroplasmy consisting of a normal 16.5-kb band and an approximately 28-kb band, suggestive of a duplication. Mitochondrial DNA analysis of a muscle biopsy of patient 2 showed multiple deletions, mainly 10- and 11-kb bands. We suggest that this unique combination of intestinal pseudo-obstruction and neurogenic bladder could comprise a new autosomal-recessive mitochondrial disorder.
Haftel
L T
LT
Pediatrics Department, Wolfson Medical Center, Holon, Israel.
Lev
D
D
Barash
V
V
Gutman
A
A
Bujanover
Y
Y
Lerman-Sagie
T
T
D000293:Adolescent; D000328:Adult; D001342:Autonomic Nervous System Diseases / Q000209:etiology; D002648:Child; D030401:Cytochrome-c Oxidase Deficiency; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007418:Intestinal Pseudo-Obstruction / Q000201:enzymology / Q000209:etiology*; D007585:Jews / Q000235:genetics; D008297:Male; D017240:Mitochondrial Myopathies / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D009130:Muscle, Smooth / Q000473:pathology; D013577:Syndrome; D001750:Urinary Bladder, Neurogenic / Q000201:enzymology / Q000209:etiology*
D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV