title: Therapeutic approaches to cobalamin-C methylmalonic acidemia and homocystinuria.
abstract: The use of hydroxocobalamin (OH-B12), betaine, carnitine, and folinic acid were studied in two children with the cobalamin C form of methylmalonic acidemia and homocystinuria. When daily injections of 1 mg OH-B12 were discontinued for 3 weeks, there was no significant change in total plasma homocysteine or methionine levels and only a modest increase in methylmalonate. Orally administered OH-B12 1 mg/d in one patient was associated with an increase in plasma homocystine and a decrease in methionine within 1 month. Withdrawal of betaine 250 mg/kg/d was also associated with a rise in plasma homocystine and a fall in methionine levels. Carnitine 100 mg/kg/d lead to an increase in urinary excretion of propionylcarnitine, but did not affect plasma methylmalonate levels. No beneficial biochemical effect of folinic acid could be documented at a dose of 25 mg/d. Our results suggest that daily injections of OH-B12 are not necessary to maintain metabolic control and that orally administered OH-B12 is unlikely to be effective. Betaine appears to act synergistically with OH-B12 and should be part of the treatment regimen. Although there are theoretical reasons for using L-carnitine and folinic acid, we could not document their effectiveness in these two patients.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: D W
authors.initials: DW
authors.lastname: Bartholomew
authors.forename: M L
authors.initials: ML
authors.lastname: Batshaw
authors.forename: R H
authors.initials: RH
authors.lastname: Allen
authors.forename: C R
authors.initials: CR
authors.lastname: Roe
authors.forename: D
authors.initials: D
authors.lastname: Rosenblatt
authors.forename: D L
authors.initials: DL
authors.lastname: Valle
authors.forename: C A
authors.initials: CA
authors.lastname: Francomano
mesh_terms: D000284:Administration, Oral; D000592:Amino Acid Metabolism, Inborn Errors / Q000188:drug therapy* / Q000378:metabolism; D001622:Betaine / Q000627:therapeutic use; D002331:Carnitine / Q000627:therapeutic use; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006712:Homocystinuria / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D006879:Hydroxocobalamin / Q000008:administration & dosage; D007223:Infant; D007273:Injections, Intramuscular; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008314:Malonates / Q000097:blood*; D008764:Methylmalonic Acid / Q000097:blood*; D014805:Vitamin B 12 / Q000378:metabolism; D014806:Vitamin B 12 Deficiency / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D008314:Malonates; D001622:Betaine; D008764:Methylmalonic Acid; D014805:Vitamin B 12; D006879:Hydroxocobalamin; D002955:Leucovorin; D002331:Carnitine