Clinicopathological features of hepatic fibrinogen storage disease in children.
10.3760/cma.j.cn112151-20210714-00506
- VernacularTitle:儿童肝脏纤维蛋白原储积病临床病理学分析
- Author:
Yuan FANG
1
;
Yi Zhen WANG
1
;
Lian CHEN
2
;
Zi Chang YIN
3
;
Jian She WANG
4
;
Xia WEI
1
;
Shao Mei LI
1
;
Xue Mei WU
1
Author Information
1. Department of Pathology, Children's Hospital of Fudan University at Anhui (Anhui Provincial Children's Hospital), Hefei 230051, China.
2. Department of Pathology, Children's Hospital of Fudan University, Shanghai 201102, China.
3. Kingmed Medical Diagnostic Center, Guangzhou 510330, China.
4. Department of Hepatology, Children's Hospital of Fudan University, Shanghai 201102, China.
- Publication Type:Review
- MeSH:
Child;
Child, Preschool;
China;
Female;
Fibrinogen/chemistry*;
Humans;
Liver/pathology*;
Liver Diseases/pathology*;
Male;
Metabolic Diseases/pathology*;
Retrospective Studies
- From:
Chinese Journal of Pathology
2022;51(4):326-331
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the clinicopathological and molecular characteristics of hepatic fibrinogen storage disease (FSD) in children. Methods: The clinical, histopathologic, immunophenotypic, ultrastructural and gene sequencing data of 4 FSD cases were collected from September 2019 to January 2021 in the Children's Hospital of Fudan University, Shanghai, China. Retrospective analysis and literature review were conducted. Results: There were 4 cases of FSD, 3 males and 1 female, aged 3 years and 3 months to 6 years (median age, 3 years and 4 months). The clinical manifestations were abnormal liver function and abnormal blood coagulation function, for which 2 cases had family genetic history. Liver biopsies revealed that, besides liver steatosis, fibrosis and inflammation, there were single or multiple eosinophilic inclusion bodies of various sizes and surrounding transparent pale halo in hepatocytes. Immunohistochemistry showed that the inclusion bodies were positive for anti-fibrinogen. Under the electron microscope, they corresponded to the dilated cisternae of the rough endoplasmic reticulum, which were occupied by compactly packed tubular structures and arranged into a fingerprint-like pattern with curved bundles. Gene sequencing revealed that the 2 cases of FGG mutation were located in exon 8 c.1106A>G (p.His369Arg) and c.905T>C (p.Leu302Pro), and 1 case was located in exon 9 c.1201C>T (p.Arg401Trp). No pathogenic variant was detected in the other case. Conclusions: FSD is a rare genetic metabolic disease and clinically manifests as abnormal liver function with hypofibrinogenemia. In the background of liver steatosis, fibrosis and inflammation, there are eosinophilic inclusions with pale halo in the hepatocytic cytoplasm, which can be identified by anti-fibrinogen immunohistochemical staining. The fingerprint-like structures under electron microscope are helpful for the diagnosis, while FGG sequencing detects the pathogenic mutation of exon 8 or 9 that can clearly explain the phenotype. However, the diagnosis of FSD cannot be completely ruled out if the relevant mutations are not detected.
