Heterozygous missense mutation of the fibrinogen gene associated with cryptogenic liver disease in a 15-months-old Canadian caucasian child

Hepatic fibrinogen storage disease is an uncommon autosomal dominant hereditary illness marked by hypofibrinogenemia and the accumulation of variant fibrinogen in the hepatic endoplasmic reticulum. We present an asymptomatic 15-month-old male with elevated liver enzymes. Test results indicate hypofibrinogenemia. The liver biopsy revealed circular eosinophilic inclusion bodies within the hepatocyte cytoplasm. After diastase pretreatment, the inclusion bodies did not stain using the periodic acid – Schiff procedure. Ultrastructural examination revealed the characteristic fibrinogen storage curvilinear inclusions. Sequence analysis using the Blueprint Genetics (BpG) FLEX Bleeding Disorder/Coagulopathy Panel identified a heterozygous missense variant <i>FGG</i> c.1075 G&gt;C, p. (Gly359Arg). Thus, the patient was diagnosed with hepatic fibrinogen storage disease. Our findings suggest that in patients with asymptomatic elevated liver enzymes presenting with unanticipated hypofibrinogenemia, hepatic fibrinogen storage disorder must be included in the differential diagnosis. Furthermore, our results underscore the significance of molecular diagnosis in patients diagnosed with cryptogenic liver disease.

肝纤维蛋白原贮积病（Hepatic fibrinogen storage disease）是一种罕见的常染色体显性遗传性疾病，以低纤维蛋白原血症（hypofibrinogenemia）及变异型纤维蛋白原在肝细胞内质网（hepatic endoplasmic reticulum）中蓄积为特征。本文报告1例无症状、肝功能酶学指标升高的15月龄男性患儿，检测结果提示其存在低纤维蛋白原血症。肝活检显示肝细胞胞质内存在圆形嗜酸性包涵体；经淀粉酶（diastase）预处理后，该包涵体无法通过过碘酸-雪夫染色法（periodic acid-Schiff procedure）着色。超微结构检查可见特征性的纤维蛋白原贮积性曲线状包涵体。使用蓝图基因（Blueprint Genetics，BpG）FLEX出血性疾病/凝血病检测面板进行序列分析，检出杂合错义变异FGG c.1075 G>C，p.(Gly359Arg)。据此，该患儿被确诊为肝纤维蛋白原贮积病。本研究结果提示，对于以无症状肝功能酶学升高伴意外发现低纤维蛋白原血症就诊的患者，需将肝纤维蛋白原贮积病纳入鉴别诊断范畴。此外，本研究结果突显了分子诊断在隐源性肝病（cryptogenic liver disease）患者中的重要意义。