Is Protein C deficiency an autosomal recessive disorder?

From the Guidelines

Protein C deficiency is typically inherited in an autosomal dominant pattern, not as a recessive condition. This means that having just one abnormal copy of the PROC gene (which provides instructions for making protein C) from either parent is sufficient to cause the disorder. People with protein C deficiency have an increased risk of developing abnormal blood clots, particularly deep vein thrombosis and pulmonary embolism. The severity varies widely, with homozygous deficiency (inheriting two abnormal copies) being extremely rare and causing severe clotting problems in newborns, while heterozygous deficiency (one abnormal copy) often causes milder symptoms that may not appear until adulthood or during high-risk situations like surgery, pregnancy, or prolonged immobility.

Key Points

• Diagnosis involves blood tests measuring protein C activity, and treatment typically includes anticoagulant medications like warfarin or direct oral anticoagulants, with dosing individualized based on severity and risk factors 1.
• During acute clotting episodes, heparin and protein C concentrate may be used.
• Family members of affected individuals should consider getting tested since this is a hereditary condition.
• Current management of protein C deficiency includes oral anticoagulants, low molecular weight heparin, and intravenous or subcutaneous protein C concentrate 1.

Considerations

• The increased risk of vascular thrombosis associated with protein C deficiency necessitates careful management and monitoring to prevent morbidity and mortality.
• Liver transplantation (LT) is curative for protein C deficiency, typically occurring in the setting of multivisceral transplantation following an abdominal catastrophe due to mesenteric vein thrombosis or renal vein thrombosis 1.

From the Research

Protein C Deficiency Inheritance

• Protein C deficiency can be inherited in an autosomal dominant manner, as seen in heterozygous individuals who are at increased risk for venous thrombosis and pulmonary embolism 2, 3, 4, 5.
• However, severe protein C deficiency, often presenting with purpura fulminans and disseminated intravascular coagulation in the neonatal period, is considered an autosomal recessive disorder 6.

Genetic Mechanisms

• The expression of protein C deficiency can be due to several genetic mechanisms, including quantitative and qualitative decreases in protein C, resulting in type I and type II deficiencies, respectively 2.
• Mutational analysis of symptomatic patients has shown a wide range of genetic mutations, contributing to the complexity of the disorder 6.

Clinical Implications

• The clinical presentation of protein C deficiency varies from asymptomatic to severe thrombotic complications, including venous thrombosis, pulmonary embolism, and purpura fulminans 2, 3, 6, 4, 5.
• Treatment of symptomatic patients typically involves anticoagulation therapy, with or without protein C replacement, to prevent and manage thrombotic events 2, 3, 6, 5.