title: Chronic disseminated intravascular coagulation and childhood-onset skin necrosis resulting from homozygosity for a protein C Gla domain mutation, Arg15Trp.
abstract: A toddler of Haitian descent presented with an 18-month history of chronic consumption coagulopathy, followed by catastrophic skin necrosis. Protein C deficiency (1% to 3% of control) was noted by functional assay; chromogenic assay and antigen levels were 30% of control. Plasma infusion abrogated the disseminated intravascular coagulation-like state. The authors identified a homozygous mutation, C1432T, resulting in a missense, Arg15Trp, in the gamma-carboxyglutamate domain of the protein. Chronic consumption coagulopathy without purpura fulminans or venous thrombosis is a rare presentation of defective protein C pathway. The result of this mutation is a mixed type I (low antigen) and type II (low function) phenotype.
authors.affiliation: Division of Hematology, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Mara
authors.initials: M
authors.lastname: Steinkamp
authors.forename: Alon
authors.initials: A
authors.lastname: Geva
authors.forename: Steven
authors.initials: S
authors.lastname: Joffe
authors.forename: Catherine N
authors.initials: CN
authors.lastname: Lapp
authors.forename: Ellis J
authors.initials: EJ
authors.lastname: Neufeld
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D016913:Blood Component Transfusion; D002908:Chronic Disease; D003646:Debridement; D004211:Disseminated Intravascular Coagulation / Q000209:etiology* / Q000628:therapy; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006720:Homozygote; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009336:Necrosis; D010641:Phenotype; D010949:Plasma; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D011486:Protein C / Q000235:genetics*; D020151:Protein C Deficiency / Q000097:blood / Q000145:classification / Q000150:complications* / Q000235:genetics / Q000473:pathology; D017434:Protein Structure, Tertiary / Q000235:genetics*; D012867:Skin / Q000098:blood supply / Q000473:pathology*; D016038:Skin Transplantation
chemical_list: D011486:Protein C