Congenital protein C deficiency is an autosomal recessive inherited coagulation condition. Patients with deficiency of protein C present with purpura fulminans or massive venous thrombosis few days or hours after birth. Patients with low levels of protein C show milder symptoms. Usually, heterozygous individuals for protein C deficiency are asymptomatic until adulthood when other risk factors such as surgery and/or pregnancy are encountered.
Diagnosis is based on the measurement of protein C levels. In severe deficiency, the protein C activity levels range from 0 to 30% and in case of partial deficiency, the level ranges from 30 to 70%. Treatment approaches include the administration of protein C concentrates or fresh frozen plasma to patients along with anticoagulant therapy and surgery when required.
Abu-Amero et al. (2003) described a 9-month-old Saudi boy who developed purpura fulminans shortly after birth. He went on to develop scrotal hematoma, following which a diagnosis of protein C deficiency was suspected. The level of protein C activity was below 0.01 U/ml (normal level 0.70–1.40 U/ml) confirming the diagnosis. The patient had hemorrhage in different tissues and organs such as in both testicles and both eyes. Magnetic resonance imaging (MRI) showed extensive bleeding on temporal occipital and parietal lobes. The patient improved on warfarin and protein C concentrate (500 units intravenously/weekly). Parents were consanguineous and the family history was negative for similar illness. A novel homozygous frame-shift mutation in the PROC gene was identified in the proband.
Alsultan et al., (2016) described two first-degree cousins affected with perinatal intracranial hemorrhage and subsequent severe thrombosis. The first case was a 10-year-old girl who presented with seizures and intracranial hemorrhage at 13 days of age. At the age of 4 months, she had multiple thrombotic lesions over both hands and feet. At 9 years of age, both protein C amidolytic activity and protein C antigen were low, 61% (nl 70–140%) and 57% (nl 70– 140%), respectively. The second case was a 2-year-old boy who presented in the first week of life with massive subacute hemorrhage in the brain parenchyma and upper spinal canal. At the age of 4 months he underwent a ventriculoperitoneal shunt because of hydrocephalus, and post operatively he had a thrombotic lesion in his left foot. At 10 months of age protein C amidolytic activity and protein C antigen were 59% and 73%, respectively. Both cases suffered from blindness and severe permanent neurological deficit. Using Exome sequencing a homozygous variant in exon 9 of PROC gene c.811 C>T was identified in both patients. The C>T polymorphism leads to the R229W amino acid change of the serine protease domain.
Al-Hamed et al. (2016) reported a 4-year-old Saudi boy affected by Thrombophilia due to Protein C Deficiency. As a neonate, the child was hospitalized for transient tachypnea and hematuria. He subsequently developed bluish swollen lesions on his arm and leg. A blood screen revealed a low platelet count and a protein C level at 0.02 U/ml (normal range 0.70–1.40 U/ml). He received a platelet transfusion and was treated with Protein C concentrate (100 IU/kg every 6 hours) until his lesions cleared. The patient was prescribed warfarin and twice-weekly infusions of protein C concentrate to manage his condition. A genetic analysis discovered a novel homozygous splice site mutation in intron 8 of the PROC gene (c.796+3A>T) that resulted in exon skipping and the creation of a pseudogene within an intron. The parents and two sisters were found to be heterozygous for the mutation.