Methaemoglobinemia Caused by Cytochrome b5 Reductase Deficiency: Genetic Studies and Long-term Treatment with Oral Methylene Blue
27th ECVIM-CA Congress, 2017
J. Jaffey1; M. Harmon1; N. Villani1; E. Creighton1; G. Johnson1; U. Giger2; J. Dodam1
1Veterinary Health Center, University of Missouri, Columbia, MO, USA; 2School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA

Methemoglobin, which cannot carry oxygen due to oxidized iron, may accumulate when the cytochrome b5 reductase system is overwhelmed by toxins or genetically dysfunctional. We report here on the diagnostic study of hereditary methemoglobinemia of a dog and a novel long-term treatment.

A juvenile male mixed breed was presented for lethargy, exercise intolerance, and aggression. Cyanosis, tachycardia, and tachypnea were observed which persisted during oxygen supplementation. Arterial blood gas analysis by co-oximetry indicated increased methemoglobin concentration (27%; normal <2%) with normal arterial oxygen tension. After initial intravenous methylene blue (MB; 1 mg/kg) administration, the dog was treated long-term with oral MB (1.5 mg/kg, q48h). Both reduced the methemoglobinemia and resolved the clinical signs during the 63-day observation period.

The erythrocytic cytochrome b5 reductase activity, measured by NADH-ferricyanide reductase assay, was low (6% compared to control), while the cytochrome c reductase activity was normal. A whole genome sequence (36x) of this dog contained two heterozygous CYB5R3 missense mutations with a serine for glycine substitution predicted at codon 72 and a leucine for isoleucine substitution predicted at codon 190. Both missense mutations are very likely to be deleterious, suggesting that each was inherited from a different parent and that each contributed to the recessive methemoglobinemia in a compound heterozygous state.

This is the first molecular genetic report of CYB5R3 variants and long-term management with oral MB of hereditary methemoglobinemia of a dog with cytochrome b5 reductase deficiency. Further studies on other affected dogs are in progress.

Disclosures

No disclosures to report.

  

Speaker Information
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J. Jaffey
Veterinary Health Center
University of Missouri
Columbia, MO, USA


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