Hereditary Erythroenzymotpathies (Schalm 29) Flashcards
What are the reactants and products of the phosphofructokinase enzymatic reaction?
Fructose-6-phosphate is additionally phosphorylated to fructose-1,6-biphosphate
What are the three isoforms of PFK?
Muscle (M-PFK)
Liver (L-PFK)
Platelet (P-PFK)
(Isoform concentrations in RBC’s is species dependent)
Canine M-PFK deficiency is present in what breed? What is the inheritance pattern?
English Springer Spaniels
Also present in cocker spaniels, whippets, and mixed breed dogs
Autosomal recessive
Under what conditions may PFK deficient dogs experience a hemolytic crisis? What is the proposed mechanism?
Alkalemia (hyperventilation) or hyperthermia may induce intravascular hemolysis
PFK deficient have decreased DPG concentrations, so chloride ions move in, increasing RBC pH, and lyse around blood pH 7.4
PFK deficient RBC’s show what change in DPG content? How is the hemoglobin-oxygen dissociation curve shifted?
Low DPG content
Shifted to the left shift and increased oxygen affinity
PFK deficiency may be confused with what other clinical disorder?
Immune mediated hemolytic anemia
What is the definitive diagnostic finding for PFK deficiency?
PFK mutation (PCR-based DNA test)
Reduced erythrocyte PFK enzyme activity
What enzymatic reaction is catalyzed by pyruvate kinase?
The ATP-generating conversion of phosphoenolpyruvate to pyruvate
Name the two genes and four isoforms of pyruvate kinase
PKLR - RBC (R-PK) and liver (L-PK) isoforms
PKM - Muscle (M1-PK, M2-PK) isoforms
What isoforms are expressed in erythrocytes, and during what maturation stages?
Erythroid precursors express M2-PK
Mature erythrocytes express R-PK almost exclusively
In what breeds has R-PK deficiency been described?
Initially Basenjis
Beagles (more frequent)
West highland white terriers, Cairn terriers, labs, pugs, min poodles, dachshunds, Chihuahuas, American Eskimo toy dogs
What effect does PK deficiency have on DPG concentrations and the hemoglobin-oxygen dissociation curve?
Increased 2,3 DPG concentrations, decreased oxygen affinity and right shift of the h-o dissociation curve
What are clinical signs of PK-deficiency in dogs?
Intermittent weakness, exercise intolerance
Severe anemia, highly regenerative with very high retic counts
Hepatosplenomegaly (EMH)
Progressive myelofibrosis and osteosclerosis d/t unknown mechanisms
What two clinical signs are strongly suggestive of PK deficiency? What confirmatory tests may be pursued?
Highly regenerative, severe anemia with osteosclerosis
PCR-based PK test kit (breed specific)
PK enzyme activity assays (cumbersome and not very accurate)
In what cat breeds has R-PK deficiency been observed?
Domestic shorthairs
Abyssinian and Somali (12% affected, 24% carriers; thus a frequent cause of anemia)
