Methylmalonic Aciduria Secondary to Selective Cobalamin Malabsorption in a Yorkshire Terrier

Abstract

An 8 wk old male Yorkshire terrier was presented with a 2 wk history of recurrent hypoglycemia, lethargy, and seizures. Investigations revealed a marked increase in blood ammonia, low serum cobalamin, and increased levels of urinary methylmalonic acid (MMA) excretion. No liver vascular abnormality was detected. The patient was diagnosed with methylmalonic aciduria due to cobalamin malabsorption. The patient responded well to parenteral cobalamin administration, and the urinary MMA levels normalized rapidly following instigation of treatment. Due to the suspected hereditary nature of selective cobalamin deficiency, one sibling of this dog was screened and found to be normal. This is the first reported case of MMA secondary to hypocobalaminemia in Yorkshire terriers, and the second report of this disease in a dog in the United Kingdom. Given the fact that clinical signs of MMA are similar to those seen in dogs with portosystemic shunts and that Yorkshire terriers are predisposed to liver vascular abnormalities, this case report adds important clinical information to the current available literature.

Review of cobalamin status and disorders of cobalamin metabolism in dogs

“…Carbamoyl phosphate synthetase I normally metabolizes ammonia to carbamoyl phosphate. When this metabolic process is impaired, plasma ammonia concentrations typically increase . Neurological disorders can thus be a complication of cobalamin deficiency states in dogs due to the increase in systemic MMA concentrations .…”

“…A genetic background for cobalamin deficiency has been confirmed or suspected in Giant Schnauzers, Border Collies, Chinese Shar‐Peis, Beagle dogs, Australian Shepherd dogs, a Yorkshire Terrier, and also a mixed breed dog (Maguire D, Solano‐Gallego L, English K, et al Cobalamin deficiency in a collie cross Bedlington Terrier. Available at: https://www.esvcp.org/index.php/docman/clin-path-cases/106-case-2-maguire-with-diagnosis/file.html); genetic defects and hypocobalaminemia has been confirmed for a few canine breeds.…”

Effects of oral versus parenteral cobalamin supplementation on methylmalonic acid and homocysteine concentrations in dogs with chronic enteropathies and low cobalamin concentrations

“…CblDef (Fyfe et al, 1991;Fordyce et al, 2000;Battersby et al, 2005;Fyfe et al, 2013;Lutz et al, 2013;Gold et al, 2015;McLauchlan et al, 2015). Furthermore, in one study, based on left-over canine serum samples submitted to a laboratory, 19% of dogs with low-normal serum cobalamin concentrations had elevated serum MMA concentrations (Berghoff et al, 2012).…”

Hereditary selective cobalamin malabsorption and concurrent pancreatitis in a young Border collie

“…Cobalamin is required for the conversion of homocysteine to methionine and for the conversion of methylmalonyl coenzyme A (CoA) to succinyl CoA; this results in accumulation of plasma homocysteine and MMA and the development of elevated plasma homocysteine levels and MMA aciduria 1 5 30. Urea cycle dysfunction and hyperammonaemia have also been described in dogs leading to neurological signs1 31 but were not reported in this case.…”

“…Weight loss occurs because decreased methionine synthase levels can lead to a deficiency in active folate which can impair DNA replication, particularly in rapidly dividing cells. This can lead to malabsorption of nutrients and reduced food intake 4 31. Interestingly, the patient had a bradyarrhythmia which was reversible with atropine; bradyarrhythmias have previously been documented in dogs with selective cobalamin malabsorption 4 11.…”