Mutation: GGG to CGG at codon 284 of the gamma chain gene (change from Gly to Arg)
Clinical and laboratory features:
(1) other family members affected
(2) low plasma fibrinogen, both antigenic and functional
(3) prolonged thrombin time suggestive of a hypodysfibrinogenemia
(4) inclusion bodies within hepatocytes, described as fiberglass-like
(4a) weakly positive on PAS staining after diastase digestion.
(4b) positive on immunohistochemical stain with antifibrinogen antibodies.
(5) Cirrhosis may occur.
Electron microscopy shows the accumulation of fibrinogen within the endoplasmic reticulum. Abnormal folding of the variant fibrinogen allows for fibrinogen-fibril formation (page 195), which causes the retention.
Dysfibrinogenemia occurs if cirrhosis develops because of hypersialylation of B-beta and gamma chains.
