Two novel homozygous mutations, G352A and C269T, are documented in the gene for deoxyguanosine kinase (DGK) in 3 children with hepatocerebral mitochondrial DNA depletion syndrome reported from Columbia University College of Physicians and Surgeons, New York; University of Pisa, Italy; University of Toronto, Canada; and University of Melbourne, Australia. All 3 patients developed liver failure and metabolic acidosis in early infancy, one also had cerebral atrophy and nystagmus, a second had microcephaly, hypotonia, and nystagmus, and a third, optic dysplasia with nystagmus and muscle involvement. DGK mutations resulted in truncated polypeptides. In patient 3, who developed multisystem disease, liver transplantation did not prevent brain dysfunction. Systemic involvement portends poor long-term prognosis. [1]
COMMENT. Mitochondrial DNA depletion syndrome can affect one, particularly muscle or liver, or multiple organs, and the liver is most frequently affected in DGK gene mutations. Primary mtDNA depletion syndrome is transmitted as an autosomal recessive trait.