Hepatic fibrinogen storage disease and hypofibrinogenemia caused by fibrinogen Aguadilla mutation: a case report.

Hepatic fibrinogen storage disease is a rare autosomal dominant genetic disorder characterized by hypofibrinogenemia, as well as the retention of variant fibrinogen within the hepatocellular endoplasmic reticulum. Here, we describe an asymptomatic 4-year-old boy with abnormal liver function test results and unexpected hypofibrinogenemia. Liver biopsy showed circular eosinophil inclusion bodies in the hepato-cytoplasm. Immunostaining results of eosinophil inclusion bodies were positive for fibrinogen. Following pretreatment with diastase, the inclusion bodies failed to stain with the periodic acid–Schiff technique; moreover, immunostaining results were positive for fibrinogen, but negative for alpha-1-antitrypsin. Genetic analysis identified a heterozygous missense mutation c.1201C > T (p. Arg401Trp) within the fibrinogen γ-chain (FGG) gene and an additional single nucleotide polymorphism c.-58 A > G within the 5′-untranslated region of the fibrinogen Aα-chain (FGA) gene. Thus, the patient was diagnosed with hepatic fibrinogen storage disease. Our results indicate that, for patients who exhibit chronic liver disease with unexpected hypofibrinogenemia, hepatic fibrinogen storage disease should be considered in the differential diagnosis. Moreover, our findings emphasize the importance of molecular diagnosis in patients with cryptogenic liver disease.