title: Protein C deficiency as the major cause of thrombophilias in childhood.
abstract: Genetic predisposition of thromboembolism depends on the racial background. Factor V Leiden (G1691A) and factor II mutation (G20210A) are the leading causes of inherited thrombophilias in Caucasians, but are not found in Asian ancestries. Protein S (PS), protein C (PC) and antithrombin (AT) activity are reportedly low in 65% of adult Japanese patients with deep vein thrombosis. Approximately half of the patients with each deficiency carry the heterozygous mutation of PS (PROS1; 20%), PC (PROC; 10%), and AT genes (SERPINC1: 5%). Recently, several studies have revealed an outline of inherited thrombophilias in Japanese children. Congenital thrombophilias in 48 patients less than age 20 years consisted of 45% PC deficiency, 15% PS deficiency and 10% AT deficiency, along with other causes. All PS- and AT-deficient patients had a heterozygous mutation of the respective gene. On the other hand, PC-deficient patients were considered to carry the homozygous or compound heterozygous mutation in 50%, the heterozygous mutation in 25%, and unknown causes in the remaining 25% of patients. Half of unrelated patients with homozygous or compound heterozygous PROC mutations carried PC-nagoya (1362delG), while their parents with its heterozygous mutation were asymptomatic. Most of the PC-deficient patients developed intracranial lesion and/or purpura fulminans within 2 weeks after birth. Non-inherited PC deficiency also conveyed thromboembolic events in early infancy. The molecular epidemiology of thrombosis in Asian children would provide a clue to establish the early intervention and optimal anticoagulant therapy in pediatric PC deficiency.
authors.affiliation: Department of Perinatal and Pediatric Medicine, Kyushu University, Fukuoka, Japan. ohgas@pediatr.med.kyushu-u.ac.jp
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.forename: Akira
authors.initials: A
authors.lastname: Ishiguro
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Midori
authors.initials: M
authors.lastname: Shima
authors.forename: Masashi
authors.initials: M
authors.lastname: Taki
authors.forename: Masatoki
authors.initials: M
authors.lastname: Kaneko
authors.forename: Kotaro
authors.initials: K
authors.lastname: Fukushima
authors.forename: Dongchon
authors.initials: D
authors.lastname: Kang
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D000293:Adolescent; D000925:Anticoagulants / Q000627:therapeutic use; D000991:Antithrombins / Q000097:blood; D001780:Blood Coagulation Tests; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D042241:Early Diagnosis; D061345:Early Medical Intervention; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D011486:Protein C / Q000378:metabolism; D020151:Protein C Deficiency / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy; D017293:Protein S / Q000378:metabolism; D018455:Protein S Deficiency / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D012016:Reference Values; D019851:Thrombophilia / Q000097:blood / Q000175:diagnosis / Q000235:genetics
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D011486:Protein C; D017293:Protein S