Protein C deficiency

Homozygous or compound heterozygous patients with plasma protein C concentrations below 25% may develop purpura fulminans, skin necrosis and disseminated intravascular coagulation at birth, while others experience thrombosis only in adulthood. Heterozygous carriers have an increased risk of venous thrombosis already in youth.

Heterozygous carriers of PROC variants with plasma protein C concentrations of 25–70% of normal occur in the general population with a frequency of 1:200–500, but are symptomatic in only 1:16,000 cases.

Protein C is encoded by the PROC gene, which consists of 9 exons. Pathogenic variants in PROC lead to reduced concentration and/or function of protein C.

Protein C deficiency is inherited in an autosomal dominant manner and is characterised by variable penetrance.

Two types of protein C deficiency are distinguished:

• Type I: simultaneous reduction of concentration and function
• Type II: normal or increased concentration with reduced function

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• Gandrille et al. 1995, Blood 86:2598