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Methemoglobinemia and Eccentrocytosis in Equine Erythrocyte Flavin Adenine Dinucleotide Deficiency

College of Veterinary Medicine, University of Florida, Gainesville, FL (JWH); College of Veterinary Medicine, University of Missouri, Columbia, MO (SLS, ¹ MAS, ^,2 PJJ, JJD ^,3); and the NIH Clinical Nutrition Research Unit, School of Medicine, University of California, Davis, CA (CJC)

This report describes erythrocyte biochemical findings in an adult Spanish mustang mare that exhibited persistent methemoglobinemia, eccentrocytosis, and pyknocytosis that were not related to the consumption or administration of an exogenous oxidant. The methemoglobinemia was attributed to a deficiency in cytochrome-b₅ reductase (Cb₅R) activity, and the eccentrocytes and pyknocytes were attributed to a marked deficiency in reduced nicotinamide adenine dinucleotide phosphate–dependent glutathione reductase (GR) activity that resulted in decreased reduced glutathione concentration within erythrocytes. The GR activity increased to a near-normal value after addition of flavin adenine dinucleotide (FAD) to the enzyme assay, indicating a deficiency of FAD in erythrocytes. The methemoglobinemia, eccentrocytosis, and pyknocytosis were attributed to deficiency of FAD in erythrocytes because the GR and Cb₅R enzymes use FAD as a cofactor. This deficiency in FAD results from a defect in erythrocyte riboflavin metabolism, which has not been documented previously in animals.

Key words: Cytochrome-b₅ reductase deficiency; eccentrocytes; erythrocytes; FAD; flavin adenine dinucleotide; glutathione reductase deficiency; methemoglobinemia; riboflavin.

Request reprints from Dr. John W. Harvey, Box 100144, Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610 (USA). E-mail: harveyj{at}mail.vetmed.ufl.edu.

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