Autosomal recessive inherited phosphofructokinase deficiency in English springer spaniel dogs

Abstract

Three families of English springer spaniel dogs with phosphofructokinase (PFK) deficiency causing haemolysis were studied. Four male dogs and one female dog with chronic haemolysis and haemolytic crises were found to have markedly reduced PFK activity in erythrocytes (8-20% of control English springer spaniels). PFK-deficient erythrocytes exhibited an extreme alkaline and sucrose lysis. The oxygen dissociation curve of erythrocyte suspensions was shifted to the left with a 50% saturation of haemoglobin at a partial oxygen pressure of 16-17 mmHg (normal 26-31 mmHg). Muscle wasting and mildly increased serum creatine phosphokinase activity were also noted. Six clinically normal first degree relatives of affected dogs had erythrocyte PFK activities that were 38-51% of controls. In these family members, there was an erythrocytosis and mild reticulocytosis probably due to a mildly enhanced haemoglobin-oxygen affinity but no increase in serum creatine phosphokinase. These studies confirm the familial nature of muscle-type PFK deficiency in English springer spaniels and support the conclusion that this animal model of the human glycogen storage disease type VII is inherited as an autosomal recessive trait.

Molecular Basis of Canine Muscle Type Phosphofructokinase Deficiency

“…The clinicopathological similarities of the exertional myopathy and erythroenzymopathy in both species have been reported (7,9). Our studies characterize the molecular basis of M-PFK deficiency in dogs and suggest that canine PFK deficiency is an excellent disease homologue to further investigate pathogenesis and novel therapeutic approaches.…”

“…The affected dogs have a chronic compensated hemolytic disorder and exertional myopathy, as is seen in human patients. However, these animals most often present with hemolytic crises due to the high capacity of the dog for aerobic work and the intrinsic alkaline fragility of erythrocytes (7). Dogs with M-PFK deficiency have 6 -22% of normal erythrocyte PFK activity and 1-4% of normal muscle PFK activity (5)(6)(7)(8)(9).…”

“…However, these animals most often present with hemolytic crises due to the high capacity of the dog for aerobic work and the intrinsic alkaline fragility of erythrocytes (7). Dogs with M-PFK deficiency have 6 -22% of normal erythrocyte PFK activity and 1-4% of normal muscle PFK activity (5)(6)(7)(8)(9). The normal canine M-PFK cDNA has been sequenced recently (10), making it possible to elucidate the underlying molecular mechanisms of canine M-PFK deficiency.…”

Biochemical Studies of Canine Muscle Phosphofructokinase Deficiency

“…An inherited muscle-type PFK deficiency in dogs has recently been recognized [2][3][4], and the present biochemical studies on skel etal muscle biopsies from PFK-deficient dogs clearly demonstrate the glycolytic de fect in muscle in vitro. The PFK activity of skeletal muscle from 4 affected dogs was only 1 % of normal, which is similar to the residual levels reported in most humans with this disorder [1,12].…”

“…Ho mozygous muscle-type PFK deficiency in humans, also known as glycogen storage dis ease type VII, causes a metabolic myopathy and compensated hemolysis [1], An autoso mal recessive inherited muscle-type PFK de ficiency was recently discovered in the dog [2][3][4], Affected animals have persistent he molysis and intermittent hemolytic crises due to low erythrocyte PFK activity (8-22% of control values), but exhibit only mild clin ical signs of myopathy such as exercise intol erance, slightly to moderately increased se…”