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mitochondrial DNA depletion syndrome


Saturday 25 June 2005

The mitochondrial DNA (mtDNA) depletion syndrome is a quantitative defect of mtDNA resulting from dysfunction of one of several nuclear-encoded factors responsible for maintenance of mitochondrial deoxyribonucleoside triphosphate (dNTP) pools or replication of mtDNA.

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).


- form hepatocerebral of autosomal recessive mitochondrial DNA depletion syndrome (MIM.251880)


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- Taanman, J.-W.; Kateeb, I.; Muntau, A. C.; Jaksch, M.; Cohen, N.; Mandel, H. : A novel mutation in the deoxyguanosine kinase gene causing depletion of mitochondrial DNA. Ann. Neurol. 52: 237-239, 2002. PubMed ID : 12210798

- Taanman, J.-W.; Muddle, J. R.; Muntau, A. C. : Mitochondrial DNA depletion can be prevented by dGMP and dAMP supplementation in a resting culture of deoxyguanosine kinase-deficient fibroblasts. Hum. Molec. Genet. 12: 1839-1845, 2003. PubMed ID : 12874104

- Tadiboyina, V. T.; Rupar, A.; Atkison, P. Feigenbaum, A.; Kronick, J.; Wang, J.; Hegele, R. A. : Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria. Am. J. Med. Genet. 135A: 289-291, 2005.