MITOCHONDRIAL DNA DEPLETION SYNDROME
General description (for patients): A defect in mitochondrial energy-producing pathways results in this progressive muscle and liver disorder. Muscles become weak and atrophic and liver failure often leads to death in the first year of life but some live for several years.
Medical description: This disease of the mitochondrial respiratory chain is progressive with primary manifestations in the liver and muscles. Generalized hypotonia and progressive liver failure are common, with many dying in infancy. Severe lactic acidosis, irritability, and muscle atrophy may be seen early.
GENETICS: A defect in the mitochondrial thymidine kinase gene (TK2) located on chromosome 16 (16q22) can be responsible for this disorder. However, two sibs (male and female) and a third unrelated child of Dutch-German Mennonite parents with this syndrome have been reported with a 255G>T substitution in another gene, deoxyguanosine kinase (DGUOK). The offspring were all homozygous and the parents heterozygous for this nuclear-encoded gene (DGUOK) supporting autosomal inheritance in spite of the gene’s expression in mitochondria. These sibs also had cystathioninuria which has not been reported in other cases.
TREATMENT: One patient improved two years after a liver transplant but long-term follow-up has not been reported.
PROGNOSIS: Death within the first two years is common but survival into the second decade of life is not uncommon.
ANCILLARY TREATMENTS AND SUPPORT: The only treatment known to have some benefit is a liver transplant as mentioned above.
SPECIALISTS AND SPECIALTY CENTERS: Pediatrician, Gastroenterologist
Tadiboyina ,V., Rupar, A., Atkison, P., Feigenbaum, A., Kronick, J., Wang, J., and Hegele, R.: Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria. Am. J. Hum. Genet. 135A: 289-291, 2005. PubMed ID: 15887277
Oskoui, M., Davidzon, G., Pascual, J., Erazo, R., Gurgel-Giannetti, J., Krishna, S., Bonilla, E., De Vivo, D. C., Shanske, S. and DiMauro, S. : Clinical spectrum of mitochondrial DNA depletion due to mutations in the thymidine kinase 2 gene. Arch. Neurol. 63: 1122-1126, 2006. PubMed ID: 16908738