Acetazolamide-responsive paroxysmal dyskinesia in a 12-week-old female golden retriever dog

Royaux, Emilie; Bhatti, Sofie; Harvey, Robert J.; Garosi, Laurent; Shelton, G. Diane; Ham, Luc Van

doi:10.1080/01652176.2015.1123822

Cited by 8 publications

(11 citation statements)

References 31 publications

(51 reference statements)

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“…16,17 The natural course of PDs was self-limiting in Labrador Retrievers and Jack Russell Terriers, with 32% of the dogs undergoing spontaneous remission and 75% showing marked improvement. 18 Several drugs have been reported to be successful in the treatment of dogs with PD, including acetazolamide, 19 fluoxetine, 20 clonazepam, 21 diazepam, 22 and phenobarbital. 23 To the our knowledge, only a single abstract (from our research group) has described this condition in Maltese dogs.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic characterization of paroxysmal dyskinesia in Maltese dogs

Polidoro

Ham

Santens

et al. 2020

Veterinary Internal Medicne

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Background Paroxysmal dyskinesias (PDs) are a group of central nervous system diseases characterized by episodes of abnormal involuntary hyperkinetic movement without altered consciousness that increasingly have been recognized in dogs. Objectives To present the phenotypical characterization, treatment, and outcome of a PD observed in Maltese dogs. Animals Client‐owned Maltese dogs (n = 19) with presumed diagnosis of PD. Methods Data were collected retrospectively from medical records (2014‐2019), and supporting information was added prospectively by using a questionnaire directed to the owners of the affected dogs. Results The episodes were characterized mainly by sudden dystonia of ≥1 limbs and generalized body tremors with preserved consciousness. The mean age of clinical onset was 5.4 years. Episode frequency varied widely both among and within individuals. Median episode duration was 4.5 minutes. Most episodes were stress‐ or exercise‐induced. Acetazolamide was administered to 6 dogs, and 4 dogs experienced a decrease in episode frequency. In 7 dogs that received a gluten‐free diet, 6 dogs became episode‐free. In 4 dogs, the episodes stopped spontaneously and in 2 dogs no medication or specific diet was given and the episodes continued at the same frequency. Conclusions and Clinical Importance Given the breed predisposition and regional distribution of the disease, additional research should focus on elucidating the underlying genetic cause doing so might advance both our understanding of the pathophysiology and treatment of this disease, not only in dogs, but also in humans. Regardless of the treatment protocol selected, prognosis appears fair to good.

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Section: Introductionmentioning

confidence: 99%

Phenotypic characterization of paroxysmal dyskinesia in Maltese dogs

Polidoro

Ham

Santens

et al. 2020

Veterinary Internal Medicne

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“…Additionally, in one dog, antiepileptic drugs of the class of carbonic anhydrase inhibitors (acetazolamide or zonisamide) were used and correlated with improved clinical signs. Successful treatment with acetazolamide has been described in Soft-coated Wheaten Terriers and Golden Retrievers with paroxysmal dyskinesia [59,60]. The exact mechanism of action is not clear yet, but it is thought that acetazolamide supports ion transport across the blood-brain barrier, modifying the intracellular pH and, therefore, the transmembrane potential, which lowers the excitability of neurons [51].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial PCK2 Missense Variant in Shetland Sheepdogs with Paroxysmal Exercise-Induced Dyskinesia (PED)

Neßler

Hug

Mandigers

et al. 2020

Genes

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Four female Shetland Sheepdogs with hypertonic paroxysmal dyskinesia, mainly triggered by exercise and stress, were investigated in a retrospective multi-center investigation aiming to characterize the clinical phenotype and its underlying molecular etiology. Three dogs were closely related and their pedigree suggested autosomal dominant inheritance. Laboratory diagnostic findings included mild lactic acidosis and lactaturia, mild intermittent serum creatine kinase (CK) elevation and hypoglycemia. Electrophysiological tests and magnetic resonance imaging of the brain were unremarkable. A muscle/nerve biopsy revealed a mild type II fiber predominant muscle atrophy. While treatment with phenobarbital, diazepam or levetiracetam did not alter the clinical course, treatment with a gluten-free, home-made fresh meat diet in three dogs or a tryptophan-rich, gluten-free, seafood-based diet, stress-reduction, and acetazolamide or zonisamide in the fourth dog correlated with a partial reduction in, or even a complete absence of, dystonic episodes. The genomes of two cases were sequenced and compared to 654 control genomes. The analysis revealed a case-specific missense variant, c.1658G>A or p.Arg553Gln, in the PCK2 gene encoding the mitochondrial phosphoenolpyruvate carboxykinase 2. Sanger sequencing confirmed that all four cases carried the mutant allele in a heterozygous state. The mutant allele was not found in 117 Shetland Sheepdog controls and more than 500 additionally genotyped dogs from various other breeds. The p.Arg553Gln substitution affects a highly conserved residue in close proximity to the GTP-binding site of PCK2. Taken together, we describe a new form of paroxysmal exercise-induced dyskinesia (PED) in dogs. The genetic findings suggest that PCK2:p.Arg553Gln should be further investigated as putative candidate causal variant.

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“…Entre los episodios la perra era completamente normal, y los resultados del hemograma, la bioquímica sanguínea y los electrólitos fueron normales. Los signos desaparecieron completamente 3 días después de comenzar la terapia con acetazolamida (Royaux et al 2016). Este caso difiere a los que presentamos en este trabajo en la ausencia de episodios de flacidez, y en la normalidad de los análisis de laboratorio.…”

Section: Discussionunclassified

Presunta parálisis periódica hipercalémica con miotonía en perros Shi-Tzú y Pastor Alemán

Pellegrino

2020

An. Vet. Murcia

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En los humanos, las canalopatías del músculo esquelético son entidades de base genética y de incidencia muy baja. En relación al canal de sodio en particular, las diferentes mutaciones SCN4A pueden dar lugar a diversos fenotipos que van desde la parálisis muscular (parálisis periódica hipercalémica, parálisis periódica hipocalémica) a la hiperexcitabilidad muscular (paramiotonía congénita, miotonías agravadas por potasio), pasando por fenotipos combinados de las dos anteriores. Existe una estrecha interrelación entre la parálisis periódica hipercalémica y las miotonías; ambas características pueden coexistir en el mismo paciente.Este trabajo describe un cuadro clínico que afectó a una camada de 7 cachorros Pastor Alemán y a una camada de 4 cachorros Shi-Tzú, con episodios caracterizados por un fenotipo clínico de parálisis muscular combinado con hiperexcitabilidad muscular.De acuerdo a los hallazgos clínicos (fenomenología clínica, edad de aparición, recurrencia de los episodios, ausencia de signos clínicos entre los episodios) y de laboratorio (hipercalemia), y a los resultados del tratamiento con acetazolamida, el diagnóstico presuntivo fue parálisis periódica hipercalémica con miotonía/paramiotonía por una canalopatía SCN4A.Destacamos la importancia del diagnóstico clínico para estas raras patologías. En ausencia de diagnóstico genético, los métodos de diagnóstico complementario tiene valor limitado debido al carácter funcional de estos trastornos.Proponemos esta comunicación como la primera de este tipo en perros de raza Pastor Alemán y Shi-Tzú. In humans, skeletal muscle channelopathies are genetic disease with very low incidence. Regarding the sodium channel in particular, the different SCN4A mutations can result in various phenotypes ranging from muscle paralysis (hyperkalemic periodic paralysis, hypokalemic periodic paralysis) to muscle hyperexcitability (congenit paramyotonia, myotonias aggravated by potassium), through combined phenotypes of the previous two. There is a close interrelation between hyperkalemic periodic paralysis and myotonias; both characteristics can coexist in the same patient.This work describes a clinical picture affecting a litter of 7 German Shepherd puppies and a litter of 4 Shih-Tzu puppies with episodes characterized by a clinical phenotype of muscular paralysis combined with muscular hyperexcitability.Based on clinical findings (clinical phenomenology, age of onset, episodic recurrence, absense of clinical signs in the period between episodes) and laboratory (hyperkalemia), and the results of treatment with acetazolamide, the presumptive diagnosis was hyperkalemic periodic paralysis with myotonia/paramyotonia due to SCN4A channelopathy.We emphasize the importance of clinical diagnosis for these rare pathologies. In absence of genetic diagnosis, complementary diagnostic methods have limited value due to the functional nature of these disorders.We proposed this description as the first communication of this type in German Shepherd and Shi-Tzu dogs.

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Acetazolamide-responsive paroxysmal dyskinesia in a 12-week-old female golden retriever dog

Cited by 8 publications

References 31 publications

Phenotypic characterization of paroxysmal dyskinesia in Maltese dogs

Phenotypic characterization of paroxysmal dyskinesia in Maltese dogs

Mitochondrial PCK2 Missense Variant in Shetland Sheepdogs with Paroxysmal Exercise-Induced Dyskinesia (PED)

Presunta parálisis periódica hipercalémica con miotonía en perros Shi-Tzú y Pastor Alemán

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