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.
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.
Authors: Laura S Kremer; Caroline L'hermitte-Stead; Pierre Lesimple; Mylène Gilleron; Sandrine Filaut; Claude Jardel; Tobias B Haack; Tim M Strom; Thomas Meitinger; Hatem Azzouz; Neji Tebib; Hélène Ogier de Baulny; Guy Touati; Holger Prokisch; Anne Lombès Journal: J Hepatol Date: 2016-05-02 Impact factor: 25.083
Authors: Min Ji Kim; Claude Jardel; Cyrille Barthélémy; Véronique Jan; Jean Philippe Bastard; Sandrine Fillaut-Chapin; Sydney Houry; Jacqueline Capeau; Anne Lombès Journal: Antimicrob Agents Chemother Date: 2008-03-10 Impact factor: 5.191
Authors: Richard H Haas; Sumit Parikh; Marni J Falk; Russell P Saneto; Nicole I Wolf; Niklas Darin; Lee-Jun Wong; Bruce H Cohen; Robert K Naviaux Journal: Mol Genet Metab Date: 2008-02-01 Impact factor: 4.797
Authors: Jean P Molleston; Ronald J Sokol; Wikrom Karnsakul; Alexander Miethke; Simon Horslen; John C Magee; René Romero; Robert H Squires; Johan L K Van Hove Journal: J Pediatr Gastroenterol Nutr Date: 2013-09 Impact factor: 2.839