To investigate clinical and genetic characteristics of neonatal congenital afibrinogenemia (CA) caused by FGG gene mutation encoding fibrinogen (Fg) γ polypeptide chain.

A baby girl with CA diagnosed and treated in Neonatology Department of Affiliated Hospital of Qingdao University in May 2021 was selected into this study. Clinical data of this girl were analyzed retrospectively. The FGG gene in peripheral blood of this neonate was detected by high-throughput sequencing of monogenic disease. Sanger sequencing of specific gene loci was performed on the parents of this neonate to identify the source of her gene mutation. The CA newborns caused by FGG gene mutation onset in neonatal period in China National Knowledge Infrastructure database, Wanfang database and PubMed database were searched, and the clinical and genetic characteristics of CA newborns were summarized. The procedure followed in this study was consistent with the requirement of Helsinki Declaration of World Medical Association revised in 2013. The guardian informed consent to the diagnosis and treatment of the infant, and signed the informed consent form of research.

① At 11.7 h after birth, this neonate (female) was admitted to hospital because of ＂facial ecchymosis for 4 h＂without bleeding in other parts of body and fever. Except facial ecchymosis, the rest of physical examination was normal. The abnormal results of routine coagulation examination at admission were mainly of antithrombin Ⅲ and plasma Fg level were lower than those normal reference parameters, which were 31.0% and 0.18 g/L, respectively; prothrombin time and thrombin time were longer than those normal reference parameters, which were 22.3 s and 24.0 s, respectively; meanwhile, plasma Fg level of her mother was also lower than normal (0.52 g/L) before giving birth, and without bleeding symptoms. ② FGG (4q28|NM_000509.4) gene exon 8: c. 1073C>A p. (Ser358Tyr) missense mutation and heterozygous mutation were detected in peripheral blood of FGG of this neonate and her mother. The mutation of FGG of this neonate came from her mother. This mutation have not been included in database, such as the human gene variation database (HGMD), etc., and reported by literature. Bioinformatics software predicted that mutation gene might have the possibility of causing disease. ③ After treated by cryoprecipitation intravenous infusion, symptom of this neonate was improved and she discharged from the hospital. Her discharge diagnosis were neonatal CA and low birth weight infant. She was follow-up to 5 months old, no bleeding symptoms were found. ④ Results of literature search: only 3 cases of CA caused by FGG gene mutation in neonatal period were found. case 1, 2 (case 1 was not described in detail, case 2 was female infant and diagnosed on 10 d old) were caused by deletion/frameshift mutation (homozygote) and the results of gene detection were FGG gene g. 194delA and FGG gene c. 1096delC mutations, clinical symptoms were umbilical cord hemorrhage or (and) articular cavity hemorrhage. Case 3 (male) from a CA pedigree caused by FGG gene mutation (mother was proband and homozygous), this newborn was heterozygote of FGG gene c. 1073C>G missense mutation and showed only mild hemorrhage.

There are few cases of CA in neonatal period, and clinical understanding of CA is insufficient. Early diagnosis of CA by detection of Fg-related genes can prevent severe life-threatening bleeding in their adulthood, such as trauma and postoperative bleeding, etc..