Congenital erythrocyte enzyme deficiencies.

Congenital hemolytic anemias resulting from PK, PFK, and G6PD enzyme deficiencies have been reported in domestic animals. Dogs with PFK deficiency may have episodes of intravascular hemolysis with hemoglobinuria in addition to a persistent compensated hemolytic anemia. Patients with mild G6PD deficiency are not anemic but may show increased susceptibility to oxidant-induced erythrocyte injury. Persistent methemoglobinemia has been reported in dogs and cats with methemoglobin reductase enzyme deficiency. Affected animals have cyanotic-appearing mucous membranes but show no or only mild clinical signs attributable to hypoxemia. Enzyme assays are usually done after acquired causes of hemolytic anemia and methemoglobinemia have been ruled out.

Equine glucose-6-phosphate dehydrogenase deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a well-characterized X-linked inherited disorder in humans but has not been reported in horses. We describe a persistent hemolytic anemia and hyperbilirubinemia due to a severe G6PD deficiency in an American Saddlebred colt. Other abnormalities in the colt's erythrocytes as compared with those of healthy horses (n = 22-35) included increased activities of hexokinase and pyruvate kinase, decreased concentrations of reduced glutathione and reduced nicotinamide adenine dinucleotide phosphate (NADP), and increased concentration of oxidized NADP. Morphologic abnormalities included eccentrocytosis, pyknocytosis, anisocytosis, macrocytosis, and increased number of Howell-Jolly bodies. Scanning and transmission electron microscopic examinations revealed that eccentrocytes had contracted to spherical regions and thin collapsed regions. Eccentrocytes were more electron dense than were normal erythrocytes when examined by transmission electron microscopy. When exposed to acetylphenylhydrazine, erythrocytes from the G6PD-deficient colt produced more and smaller Heinz bodies than did erythrocytes from normal horses. Abnormalities in the colt's dam included presence of eccentrocytes and pyknocytes; her average erythrocyte G6PD activity was slightly below the range of reference values.

Acute episodic hemolysis in the African black rhinoceros as an analogue of human glucose-6-phosphate dehydrogenase deficiency.

Sudden episodes of massive hemolysis have become the most common cause of death among captive black rhinoceroses, and there is evidence that they occur in the wild as well. We have observed radically unique enzyme and metabolite profiles in normal rhinoceros erythrocytes compared to humans and other mammals, including marked deficiencies of intracellular adenosine triphosphate (ATP), catalase, adenosine deaminase, and other enzymes involved in glycolysis, glutathione cycling, and nucleotide metabolism. Minimal concentrations of ATP appear to impair effective acceleration of hexosemonophosphate shunt activity in response to oxidants by restricting substrate generation at the hexokinase step. Antioxidant defenses are further compromised by catalase deficiency, which may be a general characteristic of rhinoceros erythrocytes, perhaps related to the common occurrence of severe mucocutaneous ulcerative disease. It is proposed that erythrocyte ATP deficiency in rhinoceroses may be an evolutionary adaptation conferring selective advantage against common hemic parasites, comparable to the role of human glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in falciparum malaria.

Glucose-6-phosphate dehydrogenase deficiency in a dog.

After screening 3,300 dogs, one animal with a mild deficiency of erythrocyte G6PD was detected. Although it had several clinical problems for 2 months, no abnormality could be directly attributable to the reduced enzymatic activity. Biochemically the mutant was electrophoretically slower but within the normal range for Km-G6P, Km-NADP, use of 2-dG6P and deamino NADP, pH optimum, and heat stability.

Glucose-6-phosphate dehydrogenase activity in erythrocytes of experimental animals.

Guinea-pigs, rats, dogs, rabbits, monkeys, sheep, and goats were screened for G-6PD activity in erythrocytes by the methaemoglobin reduction test, the brilliant cresyl blue decolorization test, and the spectrophotometric determination of the NADPH generation rate. Guinea-pigs, rats, dogs, rabbits, and monkeys were found to have normal G-6PD activity in erythrocytes, whereas sheep and goats were profoundly deficient in this enzyme. There was no evidence of any haemolytic anaemia in sheep and goats at the time of study. The relative sensitivity of these tests is discussed.