title: Mitochondrial DNA rearrangements with onset as chronic diarrhea with villous atrophy.
abstract: We report two unrelated children with onset of chronic diarrhea and villous atrophy in the first years of life. Elevated plasma lactate concentrations and lactate/pyruvate and ketone body molar ratios suggested a genetic defect of oxidative phosphorylation. Analysis of the mitochondrial respiratory chain showed a complex III deficiency in muscle of both patients. Southern blot analysis provided evidence of heteroplasmic mitochondrial DNA rearrangements that involve deletion and deletion-duplication. Directly repeated sequences (10 and 11 base pairs, respectively) were present in the wild type of mitochondrial genome at the boundaries of the deletion. Neither parent of either patient had rearranged molecules in their circulating lymphocytes. It appears that a mitochondrial disorder can have chronic diarrhea and villous atrophy as the initial clinical feature. On the basis of these observations, we suggest that genetic defects of mitochondrial energy supply be considered in elucidating the origin of unexplained chronic diarrheas, especially when other, unrelated symptoms occur in the course of the disease.
authors.affiliation: Hôpital des Enfants-Malades, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: J P
authors.initials: JP
authors.lastname: Bonnefont
authors.forename: P
authors.initials: P
authors.lastname: Rustin
authors.forename: C
authors.initials: C
authors.lastname: Maurage
authors.forename: H
authors.initials: H
authors.lastname: Ogler
authors.forename: J
authors.initials: J
authors.lastname: Schmitz
authors.forename: C
authors.initials: C
authors.lastname: Ricour
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: A
authors.initials: A
authors.lastname: Rötig
mesh_terms: D001284:Atrophy; D001483:Base Sequence; D002908:Chronic Disease; D004272:DNA, Mitochondrial; D003968:Diarrhea, Infantile / Q000201:enzymology / Q000235:genetics*; D014450:Electron Transport Complex III / Q000172:deficiency*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D007422:Intestines / Q000473:pathology*; D008969:Molecular Sequence Data; D009245:NADH Dehydrogenase / Q000378:metabolism; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D013384:Succinate Cytochrome c Oxidoreductase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III