Methemoglobinemia, Increased Deformability and Reduced Membrane Stability of Red Blood Cells in a Cat with a <i>CYB5R3</i> Splice Defect
Sophia Jenni,
Odette Ludwig-Peisker,
Vidhya Jagannathan,
Sandra Lapsina,
Martina Stirn,
Regina Hofmann-Lehmann,
Nikolay Bogdanov,
Nelli Schetle,
Urs Giger,
Tosso Leeb,
Anna Bogdanova
Affiliations
Sophia Jenni
Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland
Odette Ludwig-Peisker
Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland
Vidhya Jagannathan
Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland
Sandra Lapsina
Clinical Laboratory, Department of Clinical Diagnostics and Services, and Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland
Martina Stirn
Clinical Laboratory, Department of Clinical Diagnostics and Services, and Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland
Regina Hofmann-Lehmann
Clinical Laboratory, Department of Clinical Diagnostics and Services, and Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland
Nikolay Bogdanov
Red Blood Cell Group, Institute of Veterinary Physiology and the Center for Clinical Studies, Vetsuisse Faculty Zurich, University of Zurich, 8057 Zurich, Switzerland
Nelli Schetle
Red Blood Cell Group, Institute of Veterinary Physiology and the Center for Clinical Studies, Vetsuisse Faculty Zurich, University of Zurich, 8057 Zurich, Switzerland
Urs Giger
Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland
Tosso Leeb
Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland
Anna Bogdanova
Red Blood Cell Group, Institute of Veterinary Physiology and the Center for Clinical Studies, Vetsuisse Faculty Zurich, University of Zurich, 8057 Zurich, Switzerland
Methemoglobinemia is an acquired or inherited condition resulting from oxidative stress or dysfunction of the NADH-cytochrome b5 reductase or associated pathways. This study describes the clinical, pathophysiological, and molecular genetic features of a cat with hereditary methemoglobinemia. Whole genome sequencing and mRNA transcript analyses were performed in affected and control cats. Co-oximetry, ektacytometry, Ellman’s assay for reduced glutathione concentrations, and CYB5R activity were assessed. A young adult European domestic shorthair cat decompensated at induction of anesthesia and was found to have persistent methemoglobinemia of 39 ± 8% (reference range CYB5R3 gene, c.226+5G>A. Subsequent mRNA studies confirmed a splice defect and demonstrated expression of two mutant CYB5R3 transcripts. Erythrocytic glutathione levels were twice that of controls. Mild microcytosis, echinocytes, and multiple Ca2+-filled vesicles were found in the affected cat. Erythrocytes were unstable at high osmolarities although highly deformable as follows from the changes in elongation index and maximal-tolerated osmolarity. Clinicopathological presentation of this cat was similar to other cats with CYB5R3 deficiency. We found that methemoglobinemia is associated with an increase in red blood cell fragility and deformability, glutathione overload, and morphological alterations typical for stress erythropoiesis.
