title: How can cobalamin injections be spaced in long-term therapy for inborn errors of vitamin B(12) absorption?
abstract: Inborn errors of cobalamin (Cbl, vitamin B(12)) absorption include hereditary intrinsic factor deficiency (HIFD) and Imerslund-Gräsbeck disease (IGD). HIFD is secondary to mutations in the HIF gene while IGD is due to mutations in one of the 2 subunits of the intrinsic factor receptor that is cubilin (CUBN) or amnionless (AMN). These disorders lead to intracellular Cbl depletion which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid (MMA), and methionine depletion. The clinical presentation reflects Cbl deficiency, with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia. Mixed proteinuria, when it is present is strongly suggestive of IGD. Accurate diagnosis is always an emergency because early detection and treatment with life-long parenteral pharmacological doses of hydroxocobalamin are life saving and prevent further deterioration. However, the optimal frequency for cobalamin injections as a maintenance therapy is poorly reported. In order to evaluate the optimal maintenance schedule of cobalamin injections, we retrospectively collected clinical, biological, molecular and treatment data on 7 patients affected with congenital Cbl malabsorption. Unlike previous recommendations, we showed that a maintenance dosage of 1 mg cobalamin twice a year was enough to ensure a normal clinical status and keep the hematological and metabolic parameters in the normal range. These data suggest that patients affected with inborn errors of cobalamin absorption may be safely long-term treated with cobalamin injections every 6 months with careful follow-up of hematological and metabolic parameters. This maintenance regime is beneficial because the patients' quality of life improves.
authors.affiliation: APHP, Reference Center for Inherited Metabolic Disease, Hôpital Robert Debré, F-75019 Paris, France.
authors.forename: Amina
authors.initials: A
authors.lastname: Boina Abdallah
authors.forename: Hélène
authors.initials: H
authors.lastname: Ogier de Baulny
authors.forename: Renata
authors.initials: R
authors.lastname: Kozyraki
authors.forename: Sandrine
authors.initials: S
authors.lastname: Passemard
authors.forename: Odile
authors.initials: O
authors.lastname: Fenneteau
authors.forename: Sophie
authors.initials: S
authors.lastname: Lebon
authors.forename: Odile
authors.initials: O
authors.lastname: Rigal
authors.forename: Bettina
authors.initials: B
authors.lastname: Mesples
authors.forename: Karima
authors.initials: K
authors.lastname: Yacouben
authors.forename: Stéphane
authors.initials: S
authors.lastname: Giraudier
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Benoist
authors.forename: Manuel
authors.initials: M
authors.lastname: Schiff
mesh_terms: D000749:Anemia, Megaloblastic; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007267:Injections; D008286:Malabsorption Syndromes / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008565:Membrane Proteins; D009154:Mutation; D011506:Proteins / Q000235:genetics; D011507:Proteinuria / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000627:therapeutic use*; D014806:Vitamin B 12 Deficiency / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: C484714:AMN protein, human; D008565:Membrane Proteins; D011506:Proteins; D014805:Vitamin B 12