Complete factor H deficiency-associated atypical hemolytic uremic syndrome in a neonate.
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.
Cho
Hee Yeon
HY
Department of Pediatrics, Seoul National University Children's Hospital, 28 Yongon-dong, Chongro-gu, Seoul 110-744, South Korea.
Lee
Byong Sop
BS
Moon
Kyung Chul
KC
Ha
Il Soo
IS
Cheong
Hae Il
HI
Choi
Yong
Y
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
D015415:Biomarkers; C493495:CFH protein, human; D018389:Codon, Nonsense; D017242:Complement Factor H