title: Complete factor H deficiency-associated atypical hemolytic uremic syndrome in a neonate.
abstract: Recent advances have shown that atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. Almost 50% of cases are associated with mutations in the three complement regulatory genes, factor H (HF1), membrane co-factor protein (MCP) and factor I (IF). The corresponding gene products act in concert and affect the same enzyme, alternative pathway convertase C3bBb, which initiates the alternative pathway and amplification of the complement system. Factor H (FH) deficiency-associated aHUS usually occurs in infants to middle-aged adults and only rarely in neonates. Moreover, the vast majority of patients are heterozygous for the HF1 gene mutations. We report on a case of neonatal-onset aHUS associated with complete FH deficiency due to novel compound heterozygous mutations in the HF1 gene. A 22-day-old baby girl developed acute renal failure and a remarkably low serum complement C3 level, which was rapidly followed by the development of micro-angiopathic hemolytic anemia. Western blot analysis revealed nearly zero plasma FH levels, and an HF1 gene study showed compound heterozygous mutations, C1077W/Q1139X. Renal pathology findings were compatible with glomerular involvement in HUS. The baby recovered completely after the repetitive infusion of fresh frozen plasma. During follow-up (until she was 20 months old) after the initial plasma therapy, the disease recurred three times; twice after the tapering off of plasma therapy, and once during a weekly plasma infusion. All recurrence episodes were preceded by an upper respiratory tract infection, and were successfully managed by restarting or increasing the frequency of plasma therapy.
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, 28 Yongon-dong, Chongro-gu, Seoul 110-744, South Korea.
authors.forename: Hee Yeon
authors.initials: HY
authors.lastname: Cho
authors.forename: Byong Sop
authors.initials: BS
authors.lastname: Lee
authors.forename: Kyung Chul
authors.initials: KC
authors.lastname: Moon
authors.forename: Il Soo
authors.initials: IS
authors.lastname: Ha
authors.forename: Hae Il
authors.initials: HI
authors.lastname: Cheong
authors.forename: Yong
authors.initials: Y
authors.lastname: Choi
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D018389:Codon, Nonsense; D017242:Complement Factor H / Q000172:deficiency / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000235:genetics / Q000628:therapy; D006801:Humans; D007231:Infant, Newborn; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D020125:Mutation, Missense; D010951:Plasma Exchange / Q000379:methods; D017354:Point Mutation; D051437:Renal Insufficiency / Q000097:blood / Q000235:genetics / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C493495:CFH protein, human; D018389:Codon, Nonsense; D017242:Complement Factor H