Autosomal recessive thrombophilia due to protein S deficiency is a very rare and severe hematologic disorder resulting in thrombosis and secondary hemorrhage usually beginning in early infancy. Some affected individuals develop neonatal purpura fulminans, multifocal thrombosis, or intracranial ... Autosomal recessive thrombophilia due to protein S deficiency is a very rare and severe hematologic disorder resulting in thrombosis and secondary hemorrhage usually beginning in early infancy. Some affected individuals develop neonatal purpura fulminans, multifocal thrombosis, or intracranial hemorrhage (Pung-amritt et al., 1999; Fischer et al., 2010), whereas others have recurrent thromboses later in childhood (Comp et al., 1984). See also autosomal dominant thrombophilia due to protein S deficiency (THPH5; 612336), a less severe disorder caused by heterozygous mutation in the PROS1 gene.
Comp et al. (1984) reported 2 brothers with thrombophilia associated with homozygous protein S deficiency. Both had recurrent venous thromboses beginning in their teenage years. Laboratory studies showed no detectable protein S activity in either brother, whereas both ... Comp et al. (1984) reported 2 brothers with thrombophilia associated with homozygous protein S deficiency. Both had recurrent venous thromboses beginning in their teenage years. Laboratory studies showed no detectable protein S activity in either brother, whereas both asymptomatic parents had activities that were 15% and 30% of normal. Free protein S in the patients was essentially absent, although there was detectable protein S complexed to C4BPA (120830). Kamiya et al. (1986) observed affected persons in 3 generations of a Japanese kindred, including several persons of consanguineous parentage who had severe deficiency of protein S and were presumably homozygous for the defect. Autosomal recessive protein C deficiency (612304) has been described as the basis of neonatal purpura fulminans. Mahasandana et al. (1990) described neonatal purpura fulminans in a female Thai infant with homozygous protein S deficiency. Although there was no family history of thrombotic tendency and the parents were not known to be related, there were only trace amounts of free protein S in blood samples from the parents in initial studies. Pung-amritt et al. (1999) provided follow-up on the patient reported by Mahasandana et al. (1990). She had presented at age 10 days with neonatal purpura fulminans and later developed disseminated intravascular coagulation, which responded to cryoprecipitate transfusion. She was found to have endophthalmitis and was blind, suggesting retinal vessel thrombosis in utero. Protein S was almost undetectable in the patient's plasma. Bosson et al. (1995) described multiple thromboembolic venous occlusive complications in an 8-day-old infant who developed microthrombosis of the skin, superficial venous thrombosis, and deep venous thrombosis of the leg with a pulmonary embolism. Mintz-Hittner et al. (1999) described vitreoretinal findings similar to severe retinopathy of prematurity (ROP) in 2 sibs with complete protein S deficiency born at 40 and 34 weeks' gestation, respectively. Both parents had heterozygous protein S deficiency. Normal vasculogenesis was interrupted in both children, and only 1 of the 4 eyes retained functional vision. A normal-appearing posterior retina, normal scotopic and photopic flash electroretinograms (ERGs), and a normal flash visual evoked response were documented from the left eye of the son at 62 weeks' adjusted age. The other 3 eyes had inoperable retinal detachments and no functional vision. Mintz-Hittner et al. (1999) concluded that patients with homozygous or compound heterozygous protein S deficiency might present as infants with severe ROP. Fischer et al. (2010) reported an Albanian infant who presented on the fourth day of life with seizures and hemorrhagic shock associated with a massive intracranial bleed and laboratory evidence of disseminated intravascular coagulation. After stabilization, laboratory studies showed thrombophilia due to severe protein S deficiency (less than 10% activity). The infant later developed acute arterial thrombosis of the aorta and died on the eighth day of life. Postmortem examination showed diffuse thromboses of intracerebral capillaries, suggesting that the underlying prothrombotic condition resulted in hemorrhage.
In a Thai infant with autosomal recessive thrombophilia due to protein S deficiency (Mahasandana et al., 1990), Pung-amritt et al. (1999) identified compound heterozygosity for 2 mutations in the PROS1 gene (176880.0010 and 176880.0011). Each parent, who was ... In a Thai infant with autosomal recessive thrombophilia due to protein S deficiency (Mahasandana et al., 1990), Pung-amritt et al. (1999) identified compound heterozygosity for 2 mutations in the PROS1 gene (176880.0010 and 176880.0011). Each parent, who was found by ELISA studies to have about 50% of protein S free antigen, was heterozygous for 1 of the mutations. In an infant, born of Albanian parents, with autosomal recessive thrombophilia due to protein S deficiency, Fischer et al. (2010) identified a homozygous mutation in the PROS1 gene (176880.0012). Each parent was heterozygous for the mutation and showed about 50% protein S activity.