SystemicScedosporium prolificansinfection in an 11‐month‐old Border collie with cobalamin deficiency secondary to selective cobalamin malabsorption (canine Imerslund‐Gräsbeck syndrome)

Abstract

An 11-month-old Border collie presented collapsed and continued to deteriorate rapidly despite supportive treatment. The dog had a history of failure to thrive and recurring respiratory infection. Laboratory abnormalities included neutrophilic leucocytosis, Heinz body anaemia, hyperammonaemia, hyperbilirubinaemia, proteinuria and hypocobalaminaemia. Post-mortem examination revealed multi-focal necrosis within the heart, kidneys, pancreas, liver, meninges and cerebral cortex. Fungal hyphae in lesions were identified as Scedosporium prolificans following culture. Subsequent genotyping confirmed that the dog carried the CUBN:c.8392delC mutation in a homozygous state, verifying hereditary cobalamin deficiency (a.k.a. Imerslund-Gräsbeck syndrome). Cobalamin deficiency may have been a predisposing factor for the development of systemic fungal infection in this dog.

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.…”

“…12,15 Laboratory abnormalities consist of neutropenia, mild to moderate normocytic anemia, hyperammonemia, increased liver enzyme activities, and mild proteinuria. [8][9][10][11][12][13][14][15][16] Left untreated, IGS is life-threatening as a result of metabolic derangements and immunodeficiency. [9][10][11]16 Treatment consists of parenteral Cbl supplementation, which leads to rapid and complete clinical remission when administered sufficiently early in the course of disease, and the long-term prognosis is excellent with adequate lifelong treatment.…”

“…[8][9][10][11][12][13][14][15][16] Left untreated, IGS is life-threatening as a result of metabolic derangements and immunodeficiency. [9][10][11]16 Treatment consists of parenteral Cbl supplementation, which leads to rapid and complete clinical remission when administered sufficiently early in the course of disease, and the long-term prognosis is excellent with adequate lifelong treatment. 6,[8][9][10]12 In humans with IGS, clinical signs and biochemical variables such as MMA are monitored and usually normalize when treatment is adequate.…”