Hemolytic uremic syndrome (HUS) secondary to cobalamin C (cblC) disorder
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Diarrhea-positive hemolytic uremic syndrome (HUS) is a common cause of acute renal failure in children. Diarrhea-negative (D−), or atypical HUS, is etiologically distinct. A Medline search identified seven previously reported D− cases of HUS secondary to cobalamin C (cblC) disease presenting in infancy. An infantile presentation is reported to be associated with a high mortality rate (6/7 cases). We describe the results of a 5-year longitudinal follow-up in a child diagnosed with D− HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene. We briefly review the published experience in cblC-associated HUS to highlight the clinical characteristics of this uncommon, but potentially treatable, condition.
KeywordsHUS Cobalamin C Acute renal failure Autosomal recessive
hemolytic uremic syndrome
- MMACHC gene
methylmalonic aciduria cblC type with homocystinuria gene
von Willebrand factor-cleaving protease
We are grateful to the patient and her mother. Our sincere thanks to the staff of the Metabolic Program at the Children’s Hospital of Winnipeg (Dr. Mhanni, Tara Dzwiniel, Judy Saltel-Olson, Dr. Lorne Seargent). We thank Dr. Malcolm Ogborn (pediatric nephrologist), Dr. Charuta Joshi (pediatric neurologist), and Dr. Diane Moddemann (developmental specialist) for providing clinical care for the patient. We are grateful to Dr. David Rosenblatt and his lab (McGill Montreal) for performing the fibroblast and molecular studies.
- 1.Zimmerhackl LB, Besbas N, Jungraithmayr T, van de Kar N, Karch H, Karpman D, Landau D, Loirat C, Proesmans W, Prüfer F, Rizzoni G, Taylor MC, European Study Group for Haemolytic Uraemic Syndromes and Related Disorders (2006) Epidemiology, clinical presentation, and pathophysiology of atypical and recurrent hemolytic uremic syndrome. Semin Thromb Hemost 32:113–120PubMedCrossRefGoogle Scholar
- 12.Carmel R, Green R, Rosenblatt DS, Watkins D (2003) Update on cobalamin, folate, and homocysteine. Hematology Am Soc Hematol Educ Program:62–81Google Scholar
- 34.Linnebank M, Lutz H, Jarre E, Vielhaber S, Noelker C, Struys E, Jakobs C, Klockgether T, Evert BO, Kunz WS, Wüllner U (2006) Binding of copper is a mechanism of homocysteine toxicity leading to COX deficiency and apoptosis in primary neurons, PC12 and SHSY-5Y cells. Neurobiol Dis 23:725–730PubMedCrossRefGoogle Scholar
- 35.Cusmano- Ozog K LF, Levine S, Martin M, Nicholas E, Packman S, Rosenblatt DS, Cederbaum SD, Cowan TM, Enns GM (2007) Cobalamin C disease identified by expanded newborn screening: The California experience. Molecular genetics and metabolism. Elsevier, Nashville, pp 227–352Google Scholar
- 36.Lerner-Ellis JP, Tirone JC, Pawelek PD, Doré C, Atkinson JL, Watkins D, Morel CF, Fujiwara TM, Moras E, Hosack AR, Dunbar GV, Antonicka H, Forgetta V, Dobson CM, Leclerc D, Gravel RA, Shoubridge EA, Coulton JW, Lepage P, Rommens JM, Morgan K, Rosenblatt DS (2006) Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type. Nat Genet 38:93–100PubMedCrossRefGoogle Scholar