title: Cobalamin disorder Cbl-C presenting with late-onset thrombotic microangiopathy.
abstract: Two siblings, a boy age 12 and his sister age 4 years, presented with proteinuria and hematuria, hypertension, and chronic hemolytic anemia. At age 13 years, the boy developed an episode of severe hypertensive encephalopathy and transient renal failure. Both children are attending normal school, have no neurologic symptoms, and only minimal pigmentary retinal abnormalities. Renal biopsy showed a chronic thrombotic microangiopathic nephropathy. Both patients had hyperhomocysteinemia and mild methylmalonic aciduria. Fibroblasts showed decreased cobalamin uptake, reduced methyl- and adenosyl-cobalamin formation, and deficient incorporation of formate and propionate, compatible with the Cbl-C complementation group, but milder than that found in cells from most patients. Both patients and their father carry a balanced reciprocal translocation. Parenteral hydroxycobalamin treatment reduced the homocysteine levels, and methylmalonic acid disappeared. Increasing the dosage of hydroxycobalamin from 1 to 2.5, then 5 mg daily together with betaine, further reduced homocysteine levels (boy from 118 to 23 microM and girl from 59 to 14 microM). With this treatment, hemolysis has stopped, hematuria has disappeared, proteinuria has almost normalized, and creatinine clearance has been stable. Investigations for chronic thrombotic microangiopathy should include testing for this unusual but treatable disorder, regardless of age of presentation.
authors.affiliation: Department of Pediatrics, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium. Johan.Vanhove@uz.kuleuven.ac.be
authors.forename: Johan L K
authors.initials: JL
authors.lastname: Van Hove
authors.forename: Rita
authors.initials: R
authors.lastname: Van Damme-Lombaerts
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grünewald
authors.forename: Heidi
authors.initials: H
authors.lastname: Peters
authors.forename: Boudewijn
authors.initials: B
authors.lastname: Van Damme
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Jozef
authors.initials: J
authors.lastname: Arnout
authors.forename: Ron
authors.initials: R
authors.lastname: Wevers
authors.forename: E Regula
authors.initials: ER
authors.lastname: Baumgartner
authors.forename: Brian
authors.initials: B
authors.lastname: Fowler
mesh_terms: D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D005260:Female; D006397:Hematinics / Q000627:therapeutic use; D006417:Hematuria / Q000517:prevention & control; D006461:Hemolysis / Q000187:drug effects; D006463:Hemolytic-Uremic Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D006879:Hydroxocobalamin / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D008297:Male; D008764:Methylmalonic Acid / Q000378:metabolism; D008833:Microcirculation / Q000473:pathology; D011507:Proteinuria / Q000517:prevention & control; D013927:Thrombosis / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D014806:Vitamin B 12 Deficiency / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism
chemical_list: D006397:Hematinics; D006710:Homocysteine; D008764:Methylmalonic Acid; D006879:Hydroxocobalamin