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

Abstract

BackgroundProspective 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.ObjectivesTo 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.AnimalsSix client‐owned juvenile Beagles with genetically confirmed IGS and 28 healthy control dogs.MethodsProspective 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.ResultsAll 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 ImportanceA maintenance parenteral dose of 1 mg OH‐Cbl monthly or bimonthly appears adequate in Beagles with IGS monitored by metabolic testing.

Daily oral cyanocobalamin supplementation in Beagles with hereditary cobalamin malabsorption (Imerslund‐Gräsbeck syndrome) maintains normal clinical and cellular cobalamin status

“…In people, mutations in either the AMN or CUBN gene lead to selective Cbl malabsorption known as Imerslund‐Gräsbeck syndrome (IGS) . In dogs, selective intestinal Cbl malabsorption, comparable to IGS in humans, has been described in Australian Shepherds, Beagles, Border Collies, and Giant Schnauzers . It is an autosomal recessive trait caused by 2 distinct AMN mutations in Giant Schnauzers and Australian Shepherds, and our group and others recently identified 2 independent CUBN mutations in Border Collies and Beagles .…”

“…The condition is lethal in affected dogs unless detected and treated appropriately . Supplementation with adequate amounts of Cbl leads to rapid and complete clinical remission when Cbl is administered sufficiently early in the course of disease, and the long‐term prognosis is excellent with adequate lifelong treatment …”

“…These dogs remained clinically healthy and had urine MMA results within reference intervals (RIs) when evaluated sporadically. We recently studied the long‐term efficacy of monthly and bimonthly (every 2 months) IM Cbl injections including regular assessment of MMA as a marker of cellular Cbl availability in 6 juvenile Beagles with IGS . All dogs thrived and were clinically healthy, but the prospect of a lifelong need for IM injections prompted owners of 3 dogs to try PO Cbl supplementation.…”

Cobalaminmangel bei Hund und Katze

“…Eine allgemein anerkannte Richtlinie sowohl zur parenteralen als auch zur oralen Therapie existiert für Hund und Katze bisher nicht. Die Empfehlungen beruhen vorrangig auf empirischen Daten, mit Ausnahme je einer Studie zur parenteralen Gabe beim kaninen IGS und zur oralen Therapie beim Hund (31,46). Bei einer Therapievariante der parenteralen Gabe wird in den ersten 6 Wochen Cyanocobalamin (alternativ Hydroxycobalamin oder Adenosylcobalamin) einmal wöchentlich subkutan appliziert.…”

“…Das beschriebene Schema kommt auch beim kaninen IGS zur Anwendung, wobei sich in einer Studie aus dem Jahr 2018 eine intramuskuläre Applikation von Hydroxycobalamin im 2-monatigen Abstand als ebenso erfolgreich erwies (31). In den letzten Jahren konnte zudem gezeigt werden, dass eine erfolgreiche Supplementierung bei Hund und Katze auch mit oraler Gabe von Cobalamin möglich ist (44,45,46).…”