Pathogenesis, laboratory diagnosis, and clinical implications of erythrocyte enzyme deficiencies in dogs, cats, and horses

Abstract

Deficiencies of enzymes involved in erythrocyte metabolism can have significant effects on erythrocyte function and survival. Animals with pyruvate kinase (PK) or phosphofructokinase (PFK) deficiencies have shortened erythrocyte life spans and regenerative anemia. PK-deficient dogs (but not PK-deficient cats) develop progressive myelofibrosis and osteosclerosis of bone marrow and hemochromatosis and cirrhosis of the liver. PFK-deficient dogs have sporadic episodes of hyperventilation-induced intravascular hemolysis and hemoglobinuria. Cytochrome b5 reductase (Cb5R) deficiency in dogs and cats results in persistent methemoglobinemia and cyanotic mucous membranes. Severe deficiency of glucose-6-phosphate dehydrogenase, the rate-controlling enzyme in the pentose phosphate pathway, resulted in anemia with eccentrocytosis in an American saddlebred colt. Horses with erythrocyte flavin adenine dinucleotide (FAD) deficiency have both eccentrocytosis (attributable to severe deficiency in glutathione reductase activity) and methemoglobinemia (attributable to Cb5R deficiency); the dual enzyme deficiency occurs because FAD is a required cofactor for both enzymes. Erythrocyte enzyme deficiencies do not usually shorten life expectancy, except for PK-deficient dogs and potentially PFK-deficient dogs during a hemolytic crisis. Although enzyme deficiencies are rare causes of anemia and methemoglobinemia, the ability to diagnose deficient animals allows for the possibility of eliminating these undesirable traits in future breeding. DNA-based assays are available for PK and PFK deficiencies; whereas, biochemical tests of enzyme activity are required for other deficiencies. Continued research is needed to document additional enzyme deficiencies that likely occur and to develop additional DNA-based assays to detect heterozygous animals.

Erythrocyte pyruvate kinase deficiency in three West Highland white terriers in Ireland and the UK

“…As in previous reports, these WHWTs, initially presented with minimal clinical signs or only mild signs of exercise intolerance. The clinical findings of pale mucous membranes and hepatosplenomegaly were similar to previous reports [2,6,8,11,13-15]. Typically, review of the blood smear demonstrates evidence of enhanced erythropoiesis (polychromasia, nucleated RBCs) and echinocytes and other poikilocytes are not seen.…”

The Pathology of Comparative Animal Models of Human Haemochromatosis

“…In Basenjis and other breeds with pyruvate kinase (PK) deficiency, hepatic iron overload and fibrosis occur secondary to excessive absorption of iron from the intestine after prolonged haemolytic anaemia (Schaer and Harvey, 1992;Inal Gultekin et al, 2012). Total body iron is also increased in phosphofructokinase (PFK) deficient dogs, but liver failure as seen in PK deficient dogs has not been reported (Harvey, 2006). Secondary iron storage has also been reported in dogs following multiple blood transfusions (Sprague et al, 2003).…”

Allium species poisoning in dogs and cats

“…The former may cause a marked decrease in the activity of glucose-6-phosphate dehydrogenase (G6PD), whereas the latter can increase the methemoglobin concentration and Heinz body count in erythrocytes, and reduce glutathione concentration in the erythrocyte (30,40,41). In erythrocytes, G6PD oxidizes glutathione to a reduced form through the pentose phosphate pathway (39,42,43). When the activity of G6PD is decreased, the content of glutathione also drops, leading to increased levels of hydrogen peroxide.…”