Prospective long-term evaluation of parenteral hydroxocobalamin supplementation in juvenile beagles with selective intestinal cobalamin malabsorption (Imerslund-Gräsbeck syndrome)

J Vet Intern Med. 2018 May;32(3):1033-1040. doi: 10.1111/jvim.15090. Epub 2018 Mar 23.

Abstract

Background: Prospective studies on maintenance treatment for Beagles with hereditary selective cobalamin (Cbl) malabsorption (Imerslund-Gräsbeck syndrome, IGS) are lacking. In our experience, measurement of methylmalonic acid (MMA), a Cbl-dependent metabolite, seems more helpful to monitor Cbl status as compared with serum Cbl concentrations.

Objectives: To evaluate a standardized Cbl supplementation scheme in Beagles with IGS. We hypothesized that a single parenteral dose of 1 mg hydroxocobalamin (OH-Cbl) would maintain clinical and metabolic remission for up to 2 months.

Animals: Six client-owned juvenile Beagles with genetically confirmed IGS and 28 healthy control dogs.

Methods: Prospective study. Monthly IM OH-Cbl (1 mg) supplementation was done over a median of 9 months (range, 6-13) in 6 dogs, followed by bimonthly (every 2 months) injections in 5 dogs over a median of 6 months (range, 3-10). Health status was assessed by routine clinical examinations at injection time points and owner observations. Voided urine samples were collected immediately before OH-Cbl injections for measurement of MMA-to-creatinine concentrations using a gas-liquid chromatography-tandem mass spectrometry (GC-MS) method.

Results: All dogs were clinically healthy while receiving monthly and bimonthly OH-Cbl supplementation. Urinary MMA results in healthy dogs ranged from 1.3 to 76.5 mmol/mol creatinine (median, 2.9). Median urinary MMA concentrations did not differ between dogs with IGS receiving monthly (n = 49; 5.3 mmol/mol creatinine; range, 2.3-50.4) and bimonthly (n = 31; 5.3 mmol/mol creatinine; range, 1.6-50) injections.

Conclusions and clinical importance: A maintenance parenteral dose of 1 mg OH-Cbl monthly or bimonthly appears adequate in Beagles with IGS monitored by metabolic testing.

Keywords: dogs; methylmalonic acid; urine; vitamin B12.

MeSH terms

  • Anemia, Megaloblastic / drug therapy
  • Anemia, Megaloblastic / veterinary*
  • Animals
  • Creatinine / urine
  • Dog Diseases / drug therapy*
  • Dogs
  • Drug Administration Schedule / veterinary
  • Female
  • Hydroxocobalamin / administration & dosage
  • Hydroxocobalamin / therapeutic use*
  • Injections, Intramuscular / veterinary
  • Malabsorption Syndromes / drug therapy
  • Malabsorption Syndromes / veterinary*
  • Male
  • Methylmalonic Acid / urine
  • Prospective Studies
  • Proteinuria / drug therapy
  • Proteinuria / veterinary*
  • Vitamin B 12 / blood
  • Vitamin B 12 / urine
  • Vitamin B 12 Deficiency / drug therapy
  • Vitamin B 12 Deficiency / veterinary*

Substances

  • Methylmalonic Acid
  • Creatinine
  • Vitamin B 12
  • Hydroxocobalamin

Supplementary concepts

  • Imerslund-Grasbeck syndrome