Background/aims: The aim of this study was to delineate the specific clinical, biological and liver morphological alterations of the hepatocerebral syndrome due to alterations in the deoxyguanosine kinase gene, a rare and severe form of mitochondrial DNA depletion syndrome.
Methods: We report seven cases from three unrelated families with the same mutation in the deoxyguanosine kinase gene.
Results: All the patients presented in the first weeks of life with hepatomegaly and progressive liver failure that led to death few months later. Major psychomotor delay and multidirectional nystagmus were reported shortly after onset of the disease. Severe hyperlactacidaemia was constant. Histological examination of the liver disclosed a multifocal injury of hepatocytes with irregular foamy steatosis, cholestasis, and fibrosis, associated with different degrees of hepatosiderosis and glycogen depletion. Liver respiratory chain activities were abnormal in all analysed patients and the amount of liver mitochondrial DNA was severely decreased. An identical homozygous 4bp GATT duplication was identified in the deoxyguanosine kinase gene of all the cases.
Conclusions: These patients, together with patients reported in the literature, permit to delineate the specific features of the hepatocerebral form of mitochondrial DNA depletion syndrome and to differentiate them from other causes of neonatal liver failure.