Navajo neurohepatopathy: a mitochondrial DNA depletion syndrome?
Navajo neurohepatopathy (NNH) is an autosomal recessive disease of full-blooded Navajo children living in the Navajo Reservation of southwestern United States. Clinical features of NNH include peripheral and central nervous system involvement, acral mutilation, corneal scarring or ulceration, liver failure, and metabolic and immunologic derangement. The cause of NNH is unknown, but the clinical features of NNH are similar to those of patients with mitochondrial DNA (mtDNA) depletion. Therefore, we studied mtDNA concentration in the liver from 2 patients with NNH. Using histochemical, biochemical, and molecular techniques, we found evidence of mtDNA depletion, and we propose that the primary defect in NNH is in the nuclear regulation of mtDNA copy number.
Vu
T H
TH
Department of Neurology and H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Columbia University, New York, NY, USA. thv@aol.com
Tanji
K
K
Holve
S A
SA
Bonilla
E
E
Sokol
R J
RJ
Snyder
R D
RD
Fiore
S
S
Deutsch
G H
GH
Dimauro
S
S
De Vivo
D
D
D002950:Citrate (si)-Synthase / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006651:Histocytochemistry; D006801:Humans; D007198:Indians, North American; D007223:Infant; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008107:Liver Diseases / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D009245:NADH Dehydrogenase / Q000378:metabolism; D009422:Nervous System Diseases / Q000453:epidemiology / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism
D004272:DNA, Mitochondrial; D013384:Succinate Cytochrome c Oxidoreductase; D011451:Prostaglandin-Endoperoxide Synthases; D009245:NADH Dehydrogenase; D002950:Citrate (si)-Synthase