Neonatal-onset protein C deficiency: case report and literature review / 中国新生儿科杂志

ABSTRACT

Objective:To study the clinical features, diagnosis, treatment and genetic characteristics of neonatal-onset protein C deficiency (PCD).Methods:The clinical data of a newborn patient with severe PCD admitted to our neonatal department was reviewed. Databases including CNKI, Wanfang Database, CMB, VIP database, PubMed, Embase and SCI database were searched using" infantile", " neonate ", "newborn", "protein C deficiency" and "purpura fulminans" as key words. Published cases of PCD were analyzed.Results:The patient was a full-term female infant who developed multiple symptoms within 2 days after birth. The symptoms included thrombocytopenia, intracranial hemorrhage, purpura fulminans (PF), disseminated intravascular coagulation (DIC), celiac hemorrhage, hypertension, portal and iliac vein thrombosis, purulent meningitis and retinal detachment. Protein C activity was less than 10%. Genetic tests showed compound heterozygous mutations c.314G>T (p.c105f) of paternal origin and c.1218G>A (p.m406i) of maternal origin in PROC gene. According to ACMG guidelines, the mutations were strongly suspected pathogenic variants and consistent with an autosomal recessive (AR) inheritance pattern. The patient was discharged after 6 weeks of treatment at parents' request of withdrawal. A total of 25 articles on 29 patients with relatively complete clinical data were retrieved, including 18 males and 11 females. 4 patients were preterm and 25 full-term. 28 patients showed symptoms within 7 days after birth. The common clinical features were cutaneous PF and splanchnic thrombi. 22 cases documented protein C activity and ranged from 0 to 25%. 16 patients had PROC gene abnormalities and compound heterozygous mutations were found in 10 patients. Among the 22 patients with prognostic data, 11 died (9 within 3 months after birth), the remaining survivors suffered from sequelae including severe intellectual motor development disorder, epilepsy and blindness.Conclusions:The main clinical manifestations of neonatal-onset PCD include PF, DIC, multi-organ hemorrhage and thrombus. The disease is acute and severe, with rapid progression, poor prognosis and high fatality rate. Protein C activity and PROC gene testing may help establish the diagnosis.