The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene

Abstract

The genotype of double-PROC mutants might show less diversity than heterozygous mutants in terms of the timing of the onset of thrombophilia (newborn onset or late onset).

Diagnostic challenge of the newborn patients with heritable protein C deficiency

“…PC deficiency is the most common thrombophilia as the cause of pediatric thrombosis in Japan [28]. These patients have one allele or double allele mutations of PROC , and develop hemorrhagic infarction and/or purpura fulminans within two weeks after birth [14, 18], although thrombotic trend depends on the absolute PC activity levels [15]. Because of the varied hemostatic maturation [29], it is difficult to assess the balanced development of coagulation, anticoagulation and fibrinolysis factors during the early postnatal life.…”

“…Forty-one infants who had thrombotic events within 28 days after birth and received the genetic tests were collected from the Japanese registry for pediatric PC deficiency. Twenty-three out of 38 patients had thrombotic events and received the genetic study for PC, PS and/or AT genes at Kyushu University from 1993 to 2016, and 18 of them received the diagnosis of PC deficiency from all publications and meeting reports from 1981 to 2016 [15–21]. The information was based on the clinical network consisting of 111 perinatal care centers in Japan from 2011 to 2016.…”

“…Severe PC deficiency is a rare thrombophilia. Infants with biallelic mutations in PC gene ( PROC ) develop purpura fulminans and/or hemorrhagic stroke within 5 days after birth [15]. Perinatal stresses can also predispose the heterozygotes for PROC mutation to fetal and neonatal thromboses [16–18].…”

“…Perinatal stresses can also predispose the heterozygotes for PROC mutation to fetal and neonatal thromboses [16–18]. The ongoing cohort in Japanese children since 2011 has reported that the patients with heterozygous mutation of PROC ( n = 17, 59%) exceeded those with biallelic mutations (homozygous 3, compound heterozygous 9) in number among 29 pediatric patients who had PROC mutation(s) and thromboembolism [15–18]. However, the genetic test is an elaborative work for the early diagnosis and treatment of newborn patients with PC deficiency.…”

A novel compound heterozygous form of severe protein C deficiency causing bleeding without purpura fulminans

“…To the Editor: Heterozygous protein C (PC) deficiency is associated with increased risk of venous thromboembolism (VTE). The rare homozygous and compound heterozygous forms classically present in newborns with purpura fulminans …”