Late-onset thrombocytic microangiopathy caused by cblC disease: association with a factor H mutation

Am J Kidney Dis. 2005 Mar;45(3):588-95. doi: 10.1053/j.ajkd.2004.12.004.


Background: cblC disease is a cause of hemolytic uremic syndrome (HUS), which has been primarily described in neonates and infants with severe renal and neurological lesions.

Patients: Two sisters aged 6 and 8.5 years presented with a latent hemolytic process characterized by undetectable or low plasma haptoglobin, respectively, associated with renal failure and gross proteinuria. Renal biopsies performed in both patients found typical findings of thrombotic microangiopathy suggesting the diagnosis of HUS. Both patients were free of neurologic signs.

Results: Biochemical investigations found a cobalamin processing deficiency of the cblC type. Search for additional factors susceptible to worsen endothelial damage revealed homozygosity 677C--> T mutation in the methylenetetrahydrofolate reductase gene as well as heterozygosity for a 3254T--> C mutation in factor H in the patient with the most severe clinical presentation. Long-term subcutaneous administration of hydroxocobalamin in combination with oral betaine and folic acid resulted in clinical and biological improvement in both patients.

Conclusion: cblC disease may be a cause of chronic HUS with delayed onset in childhood. Superimposed mutation of factor H gene might influence clinical severity.

Publication types

  • Case Reports

MeSH terms

  • Anemia / etiology
  • Betaine / analogs & derivatives
  • Betaine / therapeutic use
  • Child
  • Combined Modality Therapy
  • Complement Factor H / genetics*
  • Drug Therapy, Combination
  • Endothelium, Vascular / pathology
  • Female
  • Folic Acid / therapeutic use
  • Genetic Predisposition to Disease
  • Genotype
  • Haptoglobins / deficiency
  • Hemolytic-Uremic Syndrome / drug therapy
  • Hemolytic-Uremic Syndrome / genetics*
  • Hemolytic-Uremic Syndrome / therapy
  • Humans
  • Hydroxocobalamin / therapeutic use*
  • Hypertension / etiology
  • Kidney / blood supply
  • Kidney / pathology
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Mutation, Missense
  • Nephrotic Syndrome / etiology
  • Plasma Exchange
  • Point Mutation
  • Proteinuria / etiology
  • Proto-Oncogene Proteins / deficiency*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-cbl
  • Renal Dialysis
  • Vitamin B 12 / metabolism*


  • Haptoglobins
  • Proto-Oncogene Proteins
  • complement factor H, human
  • betaine citrate
  • Betaine
  • Complement Factor H
  • Folic Acid
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Proto-Oncogene Proteins c-cbl
  • CBLC protein, human
  • Vitamin B 12
  • Hydroxocobalamin