Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven English Springer Spaniels (6 adult males and 1 female) with chronic hemolysis and sporadic intravascular hemolytic crises were determined to have a deficiency in erythrocyte phosphofructokinase (PFK) activity, a key regulatory enzyme of anaerobic glycolysis. Intermittent severe pigmenturia concomitant with weakness, lethargy, and anorexia were the major clinical signs and commonly were related to exercise or other stressful situations that caused panting or barking (hyperventilation). Pale or icteric mucous membranes, fever, mild hepatosplenomegaly, and muscle wasting sometimes were evident. Results of routine laboratory testing indicated a persistent marked bilirubinuria and reticulocytosis with normal PCV, to severe anemia and intermittent hemoglobinuria and hyperkalemia. Erythrocyte PFK activities were severely reduced to 8% to 22% of values for control dogs. The block of glycolysis at the PFK step caused a markedly diminished erythrocyte 2,3-diphosphoglycerate content, resulting in an increased hemoglobin-oxygen affinity and compensatory accelerated erythrocyte production. Phosphofructokinase-deficient erythrocytes had increased alkaline fragility in vitro and in vivo. Hemolytic crises were induced in vivo by hyperventilation that caused transient, mild alkalemia. Studies of family members of a PFK-deficient dog suggested an autosomal recessive mode of inheritance. Carrier dogs with half-normal erythrocyte PFK activities appeared clinically normal.
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PMID:Hemolysis caused by phosphofructokinase deficiency in English springer spaniels: seven cases (1983-1986). 295 37

Two male castrated Whippet littermates were presented at 1 year of age for pallor, tachycardia, systolic heart murmur, dark yellow to orange feces, intermittent lethargy, pigmenturia, and muscle shivering or cramping after exercise. Persistent macrocytic hypochromic anemia with marked reticulocytosis and metarubricytosis was found when CBC results were compared with reference values for Whippets. Increased serum creatine kinase activity and hyperkalemia also were sometimes present over the 4-year period of evaluation. Progressively increasing serum concentrations of N-terminal prohormone brain natriuretic peptide suggested cardiac disease. Erythrocytes from the whippets were less osmotically fragile but more alkaline fragile than those from control dogs. Erythrocyte phosphofructokinase (PFK) activities and 2,3-diphosphoglycerate concentrations were decreased. Restriction enzyme-based DNA test screening and DNA sequencing revealed the same mutation in the muscle-PFK gene of the Whippets as seen in English Springer Spaniel dogs with PFK deficiency. This is the first report of PFK deficiency in Whippet dogs. In addition to causing hemolysis and exertional myopathy, heart disease may be a prominent clinical component of PFK deficiency in this breed and has not been previously recognized in PFK-deficient English Springer Spaniels.
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PMID:Hemolysis, myopathy, and cardiac disease associated with hereditary phosphofructokinase deficiency in two Whippets. 1922 57