ISSN 2398-2977      

Muscle: hyperkalemic periodic paralysis

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Synonym(s): HPP, HYPP, HKPP, Impressive syndrome


Introduction

  • An autosomal inherited codominant genetic disease of Quarterhorses Quarterhorse; genetic testing suggests one particular hereditary line implicated.
  • Cause: point mutation in skeletal muscle sodium channel gene (SCN4A).
  • Signs: periodic muscle weakness; fasciculations, spasm; involuntary recumbency, stridor.
  • Diagnosis: clinical signs, blood potassium concentration Blood: biochemistry - potassium, electrocardiography (ECG) Cardiovascular: ECG (electrocardiography), electromyography (EMG) Electrodiagnostic testing, genetic testing.
  • Treatment: calcium gluconate; sodium bicarbonate and glucose to increase uptake of potassium into cells; low potassium diet to prevent episodes.
  • Prognosis: manageable disorder in most cases.

Pathogenesis

Etiology

  • The genetic defect that has been identified in this disease is only present in descendants of the American Quarter Horse Quarterhorse sire 'Impressive'. The mutation occurred naturally and was not a product of inbreeding.
  • The disease is inherited as an autosomal dominant trait and therefore occurs in both males and females. Only one copy of the mutated allele is required to produce the disease. The trait is inherited from generation to generation with equal frequency.
  • Homozygotes for gene are more severely affected than heterozygotes.
  • Most cases are reported in heterozygotes.

Pathophysiology

  • Clinical signs of the disease may be triggered by changes in management leading to stress and/or increased serum levels of potassium Potassium. There is individual variation in the likelihood of manifestation of the disease which is not currently fully understood.
  • Known trigger factors include dietary changes, high potassium diets, cold conditions, long distance transport, fasting, general anesthesia, concurrent illness, and exercise restriction.
  • Missense mutation in SCN4A produces an altered skeletal muscle sodium channel alpha chain → amino acid substitution (leucine for phenylalanine) at position 1416 of the protein product → impaired inactivation of the sodium channels → hyperkalemia.
  • Sodium channels are ‘pore-like structures’ in muscle cell membrane which control the contraction of muscle fibers. Normal muscle sodium channels are mostly closed at rest and open in response to depolarization giving rise to the early phase of the activation potential. They close and become inactivated in response to this more marked depolarization and only become responsive again once the cell has returned towards its normal resting potential in response to potassium efflux.
  • In hyperkalemic periodic paralysis, mutant defective sodium channels are more likely to open at rest, depolarizing the membrane and pushing it closer to the threshold for contraction. This makes the muscle overly excitable and more likely to contract involuntarily.
  • This allows potassium to diffuse out of the cell, potentially leading to hyperkalemia.
  • Widespread spontaneous muscle contraction gives rise to clinical signs of fasciculation and spasm of skeletal muscle. If the muscle cells become severely depolarized then the sodium channels remain inactivated, action potentials cannot be generated, and weakness ensues.
  • Cooling further depolarizes muscle membranes in horses with hyperkalemic periodic paralysis thereby increasing the likelihood of spontaneous contraction and clinical signs.
  • Hyperkalemia tends to favor development of clinical signs because it reduces the rate at which potassium can leave the cells to repolarize them following activation; it may also directly trigger mutant sodium channels to open.
  • Hyperkalemia is the major serum electrolyte abnormality during attacks and may either result from excessive dietary intake (such as fasting followed by consumption of a high potassium feed such as alfalfa) or from potassium released by spontaneously contracting muscle cells.
  • Hyperkalemia is transient, presumably because of renal clearance and redistribution into muscle cells once the attack has passed. Local warming of contracting muscles may favor hyperpolarization.
  • Hyperkalemia may affect other excitable tissues including the heart.

Timecourse

  • Usually manifests in first few days to year of life in homozygotes and at 2-5 years of age in heterozygotes.
  • Episodes last approximately 15-60 min.

Epidemiology

  • Incidence of carriers within Quarterhorse population estimated to be between 0.4% and 4.4%.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Pang D S et al (2011) Successful treatment of hyperkalaemic periodic paralysis in a horse during isoflurane anaesthesia. Vet Anaesth Analg 38 (2), 113-20 PubMed.
  • Tryon R C et al (2009) Evaluation of allele frequencies of inherited disease genes in subgroups of American Quarter Horses. JAVMA 234 (1), 120-5 PubMed.
  • Diakakis N, Spanoudes K & Dessiris A (2008) Hyperkalaemic periodic paralysis-like syndrome in a Criollo Argentino horse. Equine Vet Educ 20 (8), 396-400 VetMedResource.
  • Spier S J & Hoffman E P (2008) Hyperkalaemic periodic paralysis: Mother nature versus human nature. Equine Vet Educ 20 (8), 401-405 VetMedResource.
  • Meyrt T S, Fedde M R, Cox J H & Erickson H H (2000) Hyperkalaemic periodic paralysis in horses: a review. Equine Vet J 31(5), 362-367 PubMed.
  • Naylor J M (1997) Hyperkalemic periodic paralysis. Vet Clin North Am Equine Pract 13, 129-144 PubMed.
  • Church S (1995) Hyperkalemic periodic paralysis in Australian Quarterhorses. Aust Vet J 72 (8), 314-316 PubMed.
  • Naylor J M (1994) Equine hyperkalemic periodic paralysis - review and implications. Canadian Vet J 35, 279-285 PubMed.
  • Naylor J M, Robinson J A & Bertone J (1992) Familial incidence of hyperkalemic periodic paralysis in Quarterhorses. JAVMA 3, 340-343 PubMed.
  • Cox J H & DeBowes R M (1990) Episodic weakness caused by hyperkalemic periodic paralysis in horses. Comp Cont Educ Pract Vet (Equine) 12 (1), 83-89 VetMedResource.
  • Spier S J, Carlson G P, Holliday T A et al (1990) Hyperkalemic periodic paralysis in horses. JAVMA 197, 1009-1017 PubMed.

Other sources of information

  • American Quarterhorse Association (1996) Hyperkalemic Periodic Paralysis - A Comprehensive Brochure to Inform and Educate American Quarterhorse Enthusiasts. AQHA, PO Box 200, Amarillo, Texas 79168, USA. Tel: +1 (806) 376 4811; Website: www.aqha.com.

Organisation(s)

  • American Quarterhorse Association, PO Box 200, Amarillo, Texas 79168, USA. Tel: +1 (806) 376 4811. Website: www.aqha.com.
  • Gene probe testing: Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616-8744, USA. Website: www.vgl.ucdavis.edu

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