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

A patient with a history of diabetes mellitus and congestive heart failure was taking furosemide and metolazone as diuretics. Diabetic ketoacidosis developed, and the patient became lethargic and confused. Initial biochemical determinations showed an alkalemic pH, serum and urine ketones with an anion gap, and hyperventilation. The hyperventilation was appropriate for the degree of ketoacidosis but it was grossly inappropriate for the alkalemia. This could be explained by a direct effect of ketones on the respiratory center or a sudden increase in hydrogen ion concentration superimposed on previously chronic alkalemic pH due to the potent combination of furosemide and metolazone.
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PMID:Alkalemia in diabetic ketoacidosis. 643 81