Hepatic fibrinogen storage disease due to the fibrinogen γ375 Arg → Trp mutation "fibrinogen aguadilla" is present in Arabs

Abstract

The mutation γ375Arg → Trp (fibrinogen Aguadilla) is one of four mutations (Brescia, Aguadilla, Angers, and AI duPont) capable of causing hepatic storage of fibrinogen. It has been observed in four children from the Caribbean, Europe, and Japan, suffering from cryptogenic liver disease. We report the first case of hepatic fibrinogen storage disease in Arabs due to a mutation in the fibrinogen γ-chain gene in a 3-year-old Syrian girl presenting with elevated liver enzymes. The finding of an impressive accumulation of fibrinogen in liver cells raised the suspicion of endoplasmic reticulum storage disease. Sequencing of the fibrinogen genes revealed a γ375Arg → Trp mutation (fibrinogen Aguadilla) in the child and in her father. In conclusion, when confronted with chronic hepatitis of unknown origin, one should check the plasma fibrinogen level and look carefully for the presence of hepatocellular intracytoplasmic globular inclusions to exclude hepatic fibrinogen storage disease.

Fibrinogen storage disease and cirrhosis associated with hypobetalipoproteinemia owing to fibrinogen Aguadilla in a Turkish child

“… and Al‐Hussaini et al . . Case reports show a diverse clinical picture of HFSD in patients with the same mutation.…”

“…Originally, advanced liver disease has been described only in adult patients (6)(7)(8)(9)12). Subsequently, severe liver disease secondary to HFSD was reported in three children with fibrinogen Aguadilla mutation by Francalanci et al (13), Sogo et al (14) and Al-Hussaini et al (14,15). Case reports show a diverse clinical picture of HFSD in patients with the same mutation.…”

Fibrinogen storage disease in a Chinese boy with de novo fibrinogen Aguadilla mutation: Incomplete response to carbamazepine and ursodeoxycholic acid

“…However, only 6 mutations (listed in Table 1 , with predicted sequences) in the FGG sequence encoding the fibrinogen γ chain residues between 310 and 401 (including signal peptide) are known to cause hypofibrinogenemia and hepatocyte ER storage of abnormal fibrinogen [ 2 – 13 ]. Among them, c.1201C > T (fibrinogen Aguadilla) is repeatedly encountered [ 3 , 6 – 8 , 10 – 13 ]. It can be inherited or de novo, that is, not detected in either parent, as our patient, with genetic evidence supporting declared paternity.…”

“…FGG sequence analysis in the patient detected heterozygosity for a known disease-causing mutation (c.1201C > T/p.Arg401Trp) (Additional file 1 : Supplementary data), predicted to yield fibrinogen Aguadilla [ 3 , 6 – 8 , 10 – 13 ]. No mutation was found in either parent.…”

Hypofibrinogenemia and liver disease: a new case of Aguadilla fibrinogen and review of the literature

“…The two sons from the first Swiss family with Aguadilla have neither developed clinical symptoms of liver disease nor increased transaminase levels during a follow‐up of 9 years (personal data). Finally, the Arabic girl with Aguadilla, followed up for 8 years, was clinically asymptomatic with persistence of hypofibrinogenemia and only mild elevation of liver enzymes . Rare thromboses have been observed in FSD families .…”