hepatocerebral form of mitochondrial DNA depletion syndrome

Individuals with the hepatocerebral form of mitochondrial DNA depletion syndrome (MDDS) have early progressive liver failure and neurologic abnormalities, hypoglycemia, and increased lactate in body fluids.

Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes (I, III, IV, and V) and mtDNA depletion.

Most patients with the hepatocerebral form have a severe depletion of mtDNA (88 to 99%) in affected tissues at postmortem and usually die before 9 months of age.

The myopathic form of mtDNA depletion syndrome is a slowly progressive mitochondrial disorder starting in childhood and associated with less severe depletion of mtDNA in skeletal muscle (66 to 86%).

Navajo neurohepatopathy (NNH; MIM.256810) is also a hepatocerebral form of mtDNA depletion syndrome. The disorder in the Navajo has been shown to be due to the same missense mutation as that found in a southern Italian family with the hepatocerebral form of mtDNA depletion syndrome (MIM.137960.0001).

See also

 Alpers neuronal degeneration with hepatic disease (Alpers syndrome) (MIM.203700), a phenotypically similar disorder caused by mutations in the POLG gene (MIM.174763), and the myopathic form of mtDNA depletion syndrome (MIM.609560).

For a discussion of autosomal dominant mtDNA depletion syndrome, manifest mainly as progressive ophthalmoplegia, see PEOA1 (MIM.157640).

The autosomal recessive hepatocerebral mitochondrial DNA (mtDNA) depletion syndrome (autosomal recessive MDDS) can be caused by mutation in the nuclear-encoded mitochondrial deoxyguanosine kinase gene (DGUOK; MIM.601465), the MPV17 gene (MIM.137960), or the C10ORF2 gene (MIM.606075).