Labarthe François, Dobbelaere Dries, Devisme Louise, De Muret Anne, Jardel Claude, Taanman Jan-Willem, Gottrand Frédéric, Lombès Anne
Groupement de Médecine Pédiatrique, Hôpital Clocheville, CHU Tours, France.
J Hepatol. 2005 Aug;43(2):333-41. doi: 10.1016/j.jhep.2005.03.023.
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.
We report seven cases from three unrelated families with the same mutation in the deoxyguanosine kinase gene.
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.
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.
背景/目的：本研究旨在描述因脱氧鸟苷激酶基因改变导致的肝脑综合征的具体临床、生物学和肝脏形态学改变，这是线粒体DNA耗竭综合征的一种罕见且严重的形式。
我们报告了来自三个无亲缘关系家庭的7例患者，他们的脱氧鸟苷激酶基因存在相同突变。
所有患者在出生后的头几周出现肝肿大和进行性肝功能衰竭，数月后导致死亡。疾病发作后不久报告出现严重精神运动发育迟缓及多向性眼球震颤。持续性严重高乳酸血症。肝脏组织学检查显示肝细胞多灶性损伤，伴有不规则泡沫样脂肪变性、胆汁淤积和纤维化，伴有不同程度的肝铁沉积症和糖原耗竭。所有分析患者的肝脏呼吸链活性均异常，肝脏线粒体DNA数量严重减少。在所有病例的脱氧鸟苷激酶基因中均鉴定出相同的纯合4bp GATT重复序列。
这些患者与文献中报道的患者一起，有助于描述线粒体DNA耗竭综合征肝脑型的具体特征，并将其与新生儿肝功能衰竭的其他病因区分开来。
