Hepatic fungal infection in a young beagle with unrecognised hereditary cobalamin deficiency (Imerslund‐Gräsbeck syndrome)

Abstract

A 12-month-old beagle presented for anorexia, pyrexia and vomiting. The dog had been treated intermittently with antibiotics and corticosteroids for inappetence and lethargy since five months of age. Previous laboratory abnormalities included macrocytosis and neutropenia. At presentation, the dog was lethargic, febrile and thin. Laboratory examination findings included anaemia, a left shift, thrombocytopenia, hypoglycaemia and hyperbilirubinaemia. Multiple, small, hypoechoic, round hepatic lesions were observed on abdominal ultrasound. Cytological examination of hepatic fine needle aspirates revealed a fungal infection and associated pyogranulomatous inflammation. The dog's general condition deteriorated despite supportive measures and treatment with fluconazole, and owners opted for euthanasia before hypocobalaminaemia was identified. Subsequent genomic analysis revealed a CUBN:c.786delC mutation in a homozygous state, confirming hereditary cobalamin malabsorption (Imerslund-Gräsbeck syndrome). Similar to human infants, dogs with Imerslund-Gräsbeck syndrome may rarely be presented for infectious diseases, distracting focus from the underlying primary disorder.

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

“…Similar to infants, dogs may also be presented with more subtle clinical signs such as intermittent pyrexia, glossitis, aphthous stomatitis, and paresthesia . Laboratory abnormalities consist of neutropenia, mild to moderate normocytic anemia, hyperammonemia, increased liver enzyme activities, and mild proteinuria . Left untreated, IGS is life‐threatening as a result of metabolic derangements and immunodeficiency .…”

“…In terms of practicality, most owners of dogs with IGS in our caseload eventually switched to monthly or bimonthly IM injections of 1 mg OH‐Cbl, which appeared to be effective in the long term when assessed periodically. In Europe, genetic testing for IGS in dogs became available commercially in 2014 (http://www.laboklin.de) and for the first time allowed primary care veterinarians to diagnose the disorder before critical illness occurred . Our continuing education articles on IGS (http://www.zora.uzh.ch/id/eprint/61072/; http://www.zora.uzh.ch/id/eprint/112847/; Lutz S, Bigler B, Sewell A, Riond B, Reusch CE, Kook PH.…”

“…2 In humans, mutations in either the AMN or CUBN genes lead to selective Cbl malabsorption known as Imerslund-Gräsbeck syndrome (IGS). 3,4 In dogs, selective intestinal Cbl malabsorption, comparable to IGS in humans, has been described in Australian Shepherds, 5,6 Beagles, [7][8][9][10][11][12] Border Collies, [13][14][15][16] and Giant Schnauzers. 17 It is an autosomal recessive trait caused by 2 distinct AMN mutations in Giant Schnauzers 17 and Australian Shepherds.…”

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

“…To the authors' knowledge, this is the first report of this syndrome, confirmed by the commercially available genetic test, in Beagles from the UK that were successfully treated with parenteral cobalamin supplementation. The authors recognise that this disease has been seen in Beagles previously (Fordyce and others 2000, Barron and Wouda 2008, Fyfe and others 2014, Kook and others 2014, Kook and others 2015). …”

“…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). …”