Abstract
Background
Fibrinogen Storage Disease (FSD) is characterized by hypofibrinogenemia and hepatic inclusions due to impaired release of mutant fibrinogen causing aggregation in the hepatic endoplasmic reticulum.
Aims
Review of clinical, laboratory,histopathological findings of 2 children with FSD and a systematic review of the literature on FSD.
Methods
Medical charts of two cases were reviewed. Pubmed, Medline and Cochrane databases were searched. Search term: fibrinogen storage disease, FSD, FGG.
Results
A 5 yr old male (Patient A) and 17 month old female (Patient B) were referred to The Hospital for Sick Children for consultation of asymptomatic elevation of liver enzymes. History and physical examination were non-contributory, key lab results provided in Table 1. Work-up for other causes of liver disease was unremarkable. Liver biopsy demonstrated hepatocytes with cytoplasmic eosinophilic inclusions on H&E stain, with mild portal fibrosis (Patient A) and lobular distortion, bridging fibrosis and nodule formation with some portal inflammation (Patient B) noted. Electron microscopy showed fingerprint-like structures in the dilated cisternae of the rough ER. Genetic testing for both patients revealed Aquadilla mutation in FGG gene. Patient B received ursodeoxycholic acid (UDCA), with modest improvement in liver enzymes. At last follow-up, both are asymptomatic with persistent elevation of liver transaminases and INR, and hypofibrinogenemia. Since the first published case of FSD in 1981, there have been no deaths or liver transplants reported in the subsequent total of 19 reported cases identified (9 males, mean age15.7 yrs, range 2-64yrs from year 1981–2016). Of 6 reported mutations in FGG gene, Aguadilla was most commonly seen (9/19 cases). Severity of disease varies, with cirrhosis present in 5/19 cases. Reported treatments include UDCA (n=3), vitamin E (n=1). Carbamazepine (n=4) provides a potential autophagy-enhancing therapy based on understanding of disease mechanism. Very limited outcome data is reported with survival reported for a mean of 6.3 years in 4 cases.
Conclusions
FSD-1 is a rare liver disease in children and adults, but important because potentially treatable. We add 2 cases to the very limited published experience. We suggest that affected patients should be monitored for development of fibrosis. Treatment with carbamazepine can be considered for those with progressive disease.
Table 1: Trends in labs and TE. CB – Conjugated Bili, UCB - Unconjugated Bilirubin, TE – transient elastography
| Patient A | Time | CB (Umoll) | UCB (umol/l) | Albumin
(g/l) |
ALT
(IU/l) |
AST
(IU/l) |
INR | Fibrinogen
(g/l) |
TE |
|---|---|---|---|---|---|---|---|---|---|
| A | Baseline | 0 | 0 | 42 | 261 | 159 | 1.4 | 0.7 | - |
| A | 1yr | 0 | 0 | 38 | 144 | 99 | 1.5 | 0.9 | 3.7 |
| A | 30m | 0 | 6 | 38 | 118 | 103 | 1.3 | 1.3 | 4.6 |
| Patient B | Baseline | 0 | 0 | 40 | 117 | 209 | 1.6 | 0.6 | - |
| B | 3m | 0 | 0 | 41 | 250 | 416 | 1.6 | 0.6 | - |
| B | 1y | 0 | 0 | 42 | 126 | 93 | 1.4 | 0.9 | - |
Funding Agencies
None