Periodic hypokalaemic polymyopathy in Burmese and closely related cats

Abstract

Recent molecular genetics research has identified a single nonsense mutation in the gene (WNK4) coding for lysine-deficient 4 protein kinase, an enzyme present primarily in the distal nephron. The underlying pathomechanism in affected cats is therefore likely to be a potassium wasting nephropathy, as this enzyme is involved in complex sodium/potassium exchange mechanisms in the kidney. Additional functional characterisation of the condition is warranted to define precisely how, why and when the serum potassium concentration declines. The diagnosis of Burmese hypokalaemia is now straightforward, as an inexpensive PCR test can identify affected homozygous individuals, as well as carriers. The elimination of this condition from the Burmese breed, and also from pedigree cats infused with Burmese lines, such as the Bombay, Tonkinese and Tiffanie breeds, should therefore be possible.

A novel hypokalaemic polymyopathy and subsequent unrelated nutritional thiamine deficiency in a young Burmese cat

“…The current recommendation is to screen Burmese breeding cats with the PCR test in an attempt to eliminate the disease. 3 This cat’s presentation raises the questions of whether the genetic mutation in WNK4 is the only factor contributing to periodic hypokalaemia in this breed, and also whether closer follow-up is required in the aftermath of conditions such as pyelonephritis.…”

“… 7 The majority of cases of severe hypokalaemia are attributable to disorders affecting the renal tubules. In this case, we considered PHP 3 – a disease characterised by a genetic mutation in WNK4 , resulting in excessive potassium wasting into the urine, acute-on-chronic kidney disease with tubular interstitial nephritis, renal tubular acidosis or an as-yet-undescribed tubular defect in cats.…”

“…The appearance of the kidneys and the anamnesis (Burmese cat) lead us to suspect periodic hypokalaemic polymyopathy (PHP) of Burmese cats, 3 other renal diseases such as acute-on-chronic kidney disease with tubular interstitial nephritis and subsequent hypokalaemia, and renal tubular acidosis (previously described in isolated case reports). 4 , 5 Considering the normal blood pressure and normal adrenal glands, hyperaldosteronism was considered less likely, which was further confirmed by a normal serum aldosterone level of 234 pmol/l (RI 194–388).…”

Absence of 2899C<T Mutation in the WNK4 Gene in a Free-Ranging Lion (Panthera leo) with Polymyopathy

“…Since then, it has been reported in several countries and has been shown to be due to an autosomal recessive trait that affects young Burmese and Tonkinese cats. Affected kittens display varying degrees of weakness in the neck, thoracic limb girdle and appendicular muscles [8]. Thus far, the disease has been linked to a single nonsense mutation, producing a premature stop codon in the serinethreonine kinase gene ('with no kinase 4', WNK4) that codes for lysine-deficient 4 protein kinase [9].…”

Supernumerary maxillary fourth premolar teeth in five related Burmese cats

“…The Burmese is now one of the most genetically inbred cat populations worldwide, 3 and has been over-represented in a number of conditions, including frontonasal dysplasia (Burmese head defect), feline orofacial pain syndrome, 4 hypokalaemic polymyopathy, 5 diabetes mellitus, 6 , 7 cutaneous asthaenia, 8 endocardial fibroelastosis, 9 primary glaucoma 10 and GM2 gangliosidosis. 11 Genetic tests are available for GM2 gangliosidosis, 11 Burmese hypokalaemia 5 and Burmese head defect. 3 These genetic tests allow rapid diagnosis and treatment of affected kittens and the identification of carrier cats, which can then be excluded from the breeding population.…”