Pyruvate kinase deficiency

Pyruvate kinase deficiency (PK Def.) is caused by an inherited hemolytic disease that was described in the Abyssinian and Somali cats as well as in European shorthair cats. In PKGL-gene encoding the regulatory glycolytic enzyme pyruvate kinase, a causal mutation c.693+304G>A (Grahn et al., 2012) was found that is responsible for the development of the PK deficiency.  The mutation is located 53 nucleotides upstream of the exon 6 splice site and results in 13 bp deletion at the 3´end of exon 5 at the  mRNA-level produced in liver and blood.

Perturbation of the regulatory enzyme pyruvate kinase decreases erythrocyte longevity and results in anaemia. Additional signs include lethargy, weakness, weight loss, jaundice and abdominal enlargement.

Grahn et al. (2012) tested 14179 cats (representatives of 38 breeds or population) for the presence of causal intronic mutation. The frequency of the presence of the intronic mutation was from 0.078 % in exotic shorthair cats to 12.97 % in Bengali cats. The average frequency of the presence of the mutation in all cats tested was 9.35 %.

PK testing (genetic screening) is recommended for breeds with substantial frequency of causal mutation: Abyssinians, Somalis, Bengals, Egyptian Maus, La Perms, Maine Coon cats, Norwegian Forest cats, Savannahs, Siberians and Singapuras, as well as for any new breeds developed by crossing the afore mentioned breeds.

Very low frequency of this mutation was found in: Exotic Shorthairs, Oriental Shorthairs and Persian cats (Grahn et al. (2012).

PK Def is an autosomal recessive disorder. The disease affects cats with P/P (positive / positive) genotype only. Cats with P/N (positive /negative) genotype are clinically without any symptoms. They are genetically considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers). Because of high risk of producing affected offspring, mating of two N/P animals (carriers) can not be recommended.

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Reference:

Grahn et al.: Erythrocyte Pyruvate Kinase Deficiency mutation identified in multiple breeds of domestic cats. BMC Veterinary Research 2012 8:207.