PB0272 - Hypofibrinogenemia and liver disease: first report in a family of Greek origin

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Maria Vousvouki, Master of Science (she/her/hers)

Consultant
1st Pediatric Department Aristotle University of Thessaloniki, Greece
Thessaloniki, Thessaloniki, Greece

Co-Author(s)

AA

Alkistis Adramerina, MD Msc

Consultant
1st Pediatric Department Aristotle University of Thessaloniki, Greece
Thessaloniki, Thessaloniki, Greece
Aikaterini Teli, MD, PhD

Consultant
1st Pediatric Department Aristotle University of Thessaloniki, Greece
Thessaloniki, Thessaloniki, Greece
DP

Danai Palaiologou

Molecular biologist, geneticist
Genesis Genoma Lab, Athens, Greece
Thessaloniki, Thessaloniki, Greece
PK

Parthena Kampouridou

Consultant
Department of Pediatrics, General Hospital “G. Gennimatas”, Thessaloniki, Greece
Thessaloniki, Thessaloniki, Greece
MF

Maria Fotoulaki

Professor of Pediatrics-Pediatric Gastroenterology
4th Pediatric Department, Aristotle University of Thessaloniki, Greece
Thessaloniki, Thessaloniki, Greece
ME

Marina Economou

Professor of Pediatrics-Pediatric Haematology
1st Pediatric Department Aristotle University of Thessaloniki, Greece
Thessaloniki, Thessaloniki, Greece

Background: Hepatic fibrinogen storage disease is a rare autosomal dominant disorder caused by mutations in FGG genes. It is characterized by hypofibrinogenemia and liver disease, due to accumulation of mutant fibrinogen within the hepatocellular endoplasmic reticulum.

Aims: To report on the first Greek family to be diagnosed with an FGG mutation with distinct genotype-phenotype variation between family members.

Methods: A 23month old boy was referred for hematology consultation due to hypofrinogenemia and recurrent hypertransaminasemia. He was hospitalized before referral because of a lower respiratory tract infection, during which laboratory work up revealed hypertransaminasemia (SGOT 1336 IU/L, SGPT 1125 IU/L). The other liver biochemical markers were normal, but fibrinogen levels were undetectable. Transaminase levels started to improve 48 hours after patient’s admission. Fibrinogen levels became detectable on the 6th day of hospitalization.
During the following months the patient presented with 2 more episodes of hypofrinogenemia and hypertransaminasemia in the course of an infection. An extensive liver diagnostic work up including infectious, immunologic and metabolic parameters was negative. He was then referred for consultation. Patient’s history was unremarkable with regards to bleeding episodes and his family history was negative for both bleeding and hepatic disorders. Family laboratory work up revealed low fibrinogen levels in patient’s brother, father and uncle (from his father side) - the 2 adults reporting prior uneventful surgery. Besides the referred patient, none of the other family members presented with elevated transaminase levels or with reported episodes of transaminasemia.

Results: Genetic analysis revealed a heterozygous mutation of the FGG gene (NM_021870.3:c902G>A) resulting in arginine substitution by histidine at 301 position in the 4 male family members.

Conclusion(s): FGG gene variant c.902G>A (p.Arg301His) has been so far linked to hypo/dysfibrinogenemia. To our knowledge, this is the first report on this variation resulting in hypofibrinogenemia with liver involvement.