Pyruvate Kinase Deficiency in Miniature Schnauzers

Pyruvate kinase deficiency causes a hereditary hemolytic disorder that occurs not only in dogs, but also in humans and cats.

Pyruvate kinase (PK) is a key enzyme in anaerobic glycolysis. A deficiency of this enzyme leads to insufficient ATP production, resulting in lysis of erythrocytes or their premature destruction in the spleen. Increased red blood cell destruction clinically manifests as anemia. The lifespan of red blood cells in dogs is approximately one month; in the case of PK deficiency, erythrocyte survival is reduced to only a few days. Associated clinical signs include general weakness, increased heart rate, pale mucous membranes, impaired liver function, hepatomegaly, splenomegaly, exercise intolerance, and weight loss.

The first clinical signs appear in young dogs. Heterozygous dogs (carriers of the mutation) are usually asymptomatic, despite having approximately half the normal pyruvate kinase activity.

The causative mutation in Miniature Schnauzers is c.975G>T in the PKLR gene encoding pyruvate kinase. The mutation is inherited in an autosomal recessive manner. This means that the disease develops only in individuals that inherit the mutated gene from both parents; these individuals are designated P/P (positive/positive). Carriers of the mutated gene (N/P, i.e., negative/positive) are clinically healthy but can pass the disease to their offspring. When two heterozygous individuals (N/P) are bred, theoretically 25% of the offspring will be completely healthy, 50% will be carriers, and 25% will inherit the mutated gene from both parents and be affected by pyruvate kinase deficiency (P/P).

Since clinical signs can easily be confused with other metabolic disorders, testing for the responsible mutations in dog breeds is a suitable approach for establishing an accurate diagnosis of PK deficiency.

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Reference:

Ma, T.Y., Kuo, C.J., Liu, P.C. : From mutation to manifestation: Evaluation of a PKLR gene truncation caused by exon skipping in a Schnauzer terrier. Animals (Basel) 15:3634, 2025. Pubmed reference: 41463922