title: A case of atypical hemolytic uremic syndrome due to anti-factor H antibody in a patient presenting with a factor XII deficiency identified two novel mutations.
abstract: A 9-year-old boy with pallor and macrohematuria showed hemolytic anemia, thrombocytopenia and renal failure. There was no history of diarrhea and the stool culture was negative. A diagnosis of atypical hemolytic uremic syndrome (HUS) was confirmed; however, the cause of the prolonged activated partial thromboplastin time (APTT) was unknown. Plasma exchange and hemodialysis were performed because of progressive hemolytic anemia and renal dysfunction. Fresh frozen plasma was administered frequently to correct the prolonged APTT after hemolysis was controlled and C3 levels had recovered. Factor H (FH) and factor I (IF) levels were normal and we did not detect mutations of FH, IF and membrane cofactor protein. Further investigation revealed the presence of anti-FH antibody in the patient's plasma and a deficiency of coagulation factor XII. Analysis of the patient's coagulation system displayed <3% functional activity of factor XII, whereas levels of other coagulation factors were within the normal range. Two novel mutations (W222G and R447S) were identified upon analysis of the factor XII gene in this patient. Moreover, further investigation revealed that compound heterozygous mutations were present in two of the patient's three siblings, while the third sibling only had a mutation at W222G. The patient was treated for atypical HUS; however, no treatment was required for factor XII deficiency as he did not display a hemorrhagic tendency. We report here a rare case of atypical HUS due to anti-FH antibody presenting with a coagulation factor XII deficiency.
authors.affiliation: Department of Pediatrics, Gifu Prefectural General Medical Center, 4-6-1 Noishiki, Gifu 500-8717, Japan. mkuma@gifu-hp.jp
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsukuma
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Gotoh
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kuroyanagi
authors.forename: Takuji
authors.initials: T
authors.lastname: Yamada
authors.forename: Mitsuji
authors.initials: M
authors.lastname: Iwasa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamakawa
authors.forename: Takuhito
authors.initials: T
authors.lastname: Nagai
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Takagi
authors.forename: Hiromu
authors.initials: H
authors.lastname: Mae
authors.forename: Kenji
authors.initials: K
authors.lastname: Iijima
authors.forename: Elena
authors.initials: E
authors.lastname: Bresin
mesh_terms: D065766:Atypical Hemolytic Uremic Syndrome; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D017242:Complement Factor H / Q000276:immunology*; D005174:Factor XII / Q000235:genetics; D005175:Factor XII Deficiency / Q000235:genetics*; D006463:Hemolytic-Uremic Syndrome / Q000276:immunology / Q000628:therapy; D006801:Humans; D008297:Male; D009154:Mutation; D010314:Partial Thromboplastin Time; D006435:Renal Dialysis
chemical_list: D001323:Autoantibodies; D017242:Complement Factor H; D005174:Factor XII