Navajo neurohepatopathy: A mitochondrial DNA depletion syndrome?

Navajo neurohepatopathy (NNH) is an autosomal recessive disease of full-blo oded Navajo children living in the Navajo Reservation of southwestern Unite d States. Clinical features of NNH include peripheral and central nervous s ystem involvement, acral mutilation, corneal scarring or ulceration, liver failure, and metabolic and immunologic derangement. The cause of NNH is unk nown, but the clinical features of NNH are similar to those of patients wit h mitochondrial DNA (mtDNA) depletion. Therefore, we studied mtDNA concentr ation in the liver from 2 patients with NNH. Using histochemical, biochemic al, and molecular techniques, we found evidence of mtDNA depletion, and we propose that the primary defect in NNH is in the nuclear regulation of mtDN A copy number.