Skip to
  1. Homepage
  2. Rare diseases
  3. Search
Simple search

Simple search

*
(*) mandatory field





 

Other search option(s)

Hereditary thrombophilia due to congenital protein C deficiency

Orpha number ORPHA745
Synonym(s) Hereditary thrombophilia due to PC deficiency
Prevalence 1-9 / 1 000 000
Inheritance
  • Autosomal recessive
Age of onset Childhood
ICD-10
  • D68.2
OMIM
UMLS -
MeSH -
MedDRA -
SNOMED CT
  • 439274008

Summary

Congenital protein C deficiency is an inherited coagulation disorder characterized by deep venous thrombosis symptoms due to reduced synthesis and/or activity levels of protein C. Prevalence of severe protein C deficiency (homozygous or compound heterozygous forms) is estimated at 1/ 500,000. Partial deficiencies (heterozygous forms) are much more frequent (1/200-1/500). Men and women are equally affected. Patients with undetectable protein C levels usually manifest the disease several hours to days after birth, with purpura fulminans (see this term) or massive venous thrombosis. Purpura fulminans is a life-threatening condition involving severe clotting throughout the body and causing necrosis of tissues. Patients with low but detectable protein C levels have milder symptoms generally similar to those of heterozygous individuals. Usually, patients with heterozygous protein C deficiency are asymptomatic until adulthood. Thrombotic episodes are mainly provoked by other risk factors such as surgery, pregnancy or immobilization. Deep vein thrombosis of the lower limbs with or without pulmonary embolism is the most common manifestation of the disease. Cerebral or mesenteric venous thrombosis may also occur. Protein C deficiency is caused by mutations in the PROC (2q13-q14) gene controlling the production of protein C. Transmission is autosomal recessive. Diagnosis is based on the measurement of protein C levels. Protein C activity levels range from 0 to 30% in case of severe deficiencies and from 30 to 70% in case of partial defects. There are two biological forms of the disease. Type I deficiency is characterized by concordant reduction in protein C activity and antigen. In type II deficiency, protein C activity is reduced but protein C antigen is normal. Molecular testing is available, but is unnecessary for diagnosis. Differential diagnoses include other inherited thrombophilias including antithrombin and protein S deficiencies (see these terms). Antenatal diagnosis is feasible for families with affected children and is based on the identification of the causal mutation on DNA obtained by chorionic villus sampling. Administration of protein C concentrates or fresh frozen plasma is critical for the initial treatment of neonatal purpura fulminans. Surgical procedures may be required for excision of thrombotic lesions. Patients with thromboses are treated with anticoagulant therapy (heparin, warfarin). Attention should be paid to the risk of coumarin-induced skin necrosis. Preventive treatment is indicated in cases with a strong positive family history of thrombotic diseases, during the peripartum period or perioperatively. Prognosis may be severe in homozygous or compound heterozygous patients. Prognosis is good for heterozygous patients. With adequate treatment and monitoring, the risk of thromboembolic disease is markedly reduced. Mortality may result from pulmonary embolism.

Expert reviewer(s)

  • Pr Jenny GOUDEMAND

(*) Required fields.

Attention: Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed.


Captcha image
The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.