Hyperammonaemic encephalopathy secondary to selective cobalamin deficiency in a juvenile Border collie

Abstract

An eight-month-old Border collie was presented with anorexia, cachexia, failure to thrive and stupor. Laboratory tests demonstrated a mild anaemia, neutropenia, proteinuria and hyperammonaemia. Serum bile acid concentrations were normal, but an ammonia tolerance test (ATT) was abnormal. The dog responded to symptomatic therapy for hepatoencephalopathy. When a low serum cobalamin (vitamin B12) concentration and methylmalonic aciduria were noted, the dog was given a supplement of parenteral cobalamin. Two weeks later, a repeat ATT was normal. Cobalamin supplementation was continued every two weeks, and all clinical signs, except for proteinuria, resolved despite withdrawing all therapy for hepatoencephalopathy. A presumptive diagnosis of hereditary selective cobalamin malabsorption was made, based on the young age, Border collie breed, low serum cobalamin concentration and methylmalonic aciduria. Although hereditary selective cobalamin malabsorption in Border collies, giant schnauzers, Australian shepherd dogs and beagles has previously been reported in North America, to the authors' knowledge this is the first report of the condition in the UK and the first to document an abnormal ATT in a cobalamin-deficient dog.

Congenital cobalamin malabsorption (Imerslund‐Gräsbeck syndrome) in two Beagles in the UK

“…Both cases presented with normocytic, normochromic, non-regenerative anaemia, compatible with previous reports in hypocobalaminaemic Beagles (Fordyce and others 2000, Fyfe and others 2014) and Border collies (Battersby and others 2005, Lutz and others 2013). Case 1 also had thrombocytopenia with hypersegmented neutrophils seen on examination of mesenteric lymph node aspirates.…”

“…Cerebrospinal fluid and synovial fluid were not sampled in Case 1 because of concurrent thrombocytopenia, but a diagnosis of inflammatory meningitis or arthropathy seems unlikely based on the rapid complete response to cobalamin supplementation. Finally, another sign that both sets of owners described was lethargy, and this sign has been described in both Beagles and other breeds with hypocobalaminaemia (Morgan and others 1999, Battersby and others 2005, Lutz and others 2013, Kook and others 2015). …”

Degenerative Liver Disease in Young Beagles with Hereditary Cobalamin Malabsorption Because of a Mutation in the Cubilin Gene

“…This is a rare autosomal recessive disorder which, if left untreated, results in failure to thrive, megaloblastic anemia, proteinuria, and neurological damage 2. In dogs, primary cobalamin malabsorption, which is analogous to IGS in humans, has been reported in young Australian Shepherds,3 a Beagle,4 Border Collies,5, 6, 7 and Giant Schnauzers 8. The genetic defects in affected Border Collies and Beagles recently have been identified as 2 independent mutations in the CUBN gene 9, 10.…”

“…The genetic defects in affected Border Collies and Beagles recently have been identified as 2 independent mutations in the CUBN gene 9, 10. Similar to human patients, dogs typically present at a young age with inappetence, weakness, and failure to thrive 4, 5, 6, 8, 11. Although liver disease is recognized in cobalamin‐deficient farm animals, especially lambs,12, 13 it has not been reported in dogs suffering from hereditary cobalamin malabsorption.…”

Inherited metabolic disease in companion animals: Searching for nature’s mistakes

“…As previously reported by Fordyce et al (2000), this patient was successfully treated by parenteral vitamin B12 administration every 2-4 weeks. Cobalamin malabsorption has also been described in giant Schnauzers (Fyfe et al, 1991), Border collies (Battersby et al, 2005), and Australian shepherd dogs (He et al, 2005). Investigations of affected Giant schnauzers and Australian shepherd dogs at the molecular level (Fyfe et al, 2004;He et al, 2005) have confirmed that this disease is a true homologue of congenital megaloblastic anaemia due to vitamin B12 deficiency because of a defect in the vitamin B12/intrinsic factor receptor (Imerslund-Gräsbeck syndrome) in humans.…”