Clinical utility gene card for McArdle disease

Taylor, Rhonda L.; Davis, Mark; Turner, Emma; Brull, Astrid; Pinós, Tomàs; Cabrera, Macarena; Nowak, Kristen J.

doi:10.1038/s41431-017-0070-6

Cited by 5 publications

(5 citation statements)

References 24 publications

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“… C) Normal . Aquí cabe tener en cuenta algunas miopatías, como las 10 seleccionadas, que también pueden manifestar inicialmente una intolerancia al ejercicio [ 32 ]. Se sospecharán al aparecer grados sutiles de debilidad, atrofia, pseudohipertrofia de las pantorrillas, escápulas aladas o ‘rippling’ , junto con parámetros de CK y EMG.…”

Section: Discussionunclassified

Enfermedad de McArdle en cuatro pacientes pediátricos. Algoritmo diagnóstico ante una intolerancia al ejercicio

Vidal-Sanahuja¹,

Ortez-González²,

Nascimento-Osorio³

et al. 2022

RevNeurol

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Introducción. La enfermedad de McArdle está causada por una mutación en el gen PYGM y déficit de miofosforilasa muscular, resultando alterada la liberación de glucosa-1-P a partir del glucógeno. Suele manifestarse en la infancia con cansancio precoz y excesivo, mialgias, calambres y contracturas o rabdomiólisis, aunque no suele diagnosticarse hasta la etapa adulta. La creatincinasa se incrementa durante el ejercicio. Se presentan cuatro pacientes pediátricos, se resume la fisiopatología y se propone un algoritmo diagnóstico. Pacientes y métodos. Pacientes con edades entre 6 y 14 años. Se describe la anamnesis, la exploración física, la bioquímica, el electromiograma, el test de isquemia y el estudio genético, con biopsia muscular a un solo paciente. Se elabora un algoritmo a partir del test de isquemia. Resultados. En los tres varones, las mialgias aparecieron tras finalizar cada sesión deportiva, con un fenómeno second wind en un caso. Se apreció un test de isquemia sin elevación del lactato y marcada elevación del amonio en todos, una biopsia muscular con depósitos de glucógeno y ausencia de miofosforilasa, y gen PYGM con mutaciones homocigotas en todos. El tratamiento dietético les atenuó la sintomatología durante los ejercicios aeróbicos. Conclusiones. El test de isquemia resultó muy útil para demostrar una disfunción en la glucólisis anaeróbica. Se destaca que el suplemento oral de glucosa es muy útil para la enfermedad de McArdle, pero está contraindicado en los seis defectos de la glucólisis anaeróbica. El algoritmo también permite orientar el defecto de 20 miopatías metabólicas o estructurales, que se resumen.

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Section: Discussionunclassified

Enfermedad de McArdle en cuatro pacientes pediátricos. Algoritmo diagnóstico ante una intolerancia al ejercicio

Vidal-Sanahuja¹,

Ortez-González²,

Nascimento-Osorio³

et al. 2022

RevNeurol

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“…Sir, Glycogen storage disease V; GSD5 (MIM # 232600), also known as McArdle disease, is an autosomal recessive disorder of skeletal muscle carbohydrate metabolism due to the deficiency of the muscle specific glycogen phosphorylase, coded by the PYGM gene (MIM * 608455) for the breakdown of glycogen in skeletal muscles. 1 It is one of the most common glycogen storage disorders in Caucasian populations, with an estimated prevalence of 1 in 100,000 in the United States, or even up to 1 in 42,355 using variant frequency from exome sequencing. However, information on this condition in East Asian populations is relatively limited, with sparse reports on East Asian patients.…”

Section: Conflicts Of Interest and Sources Of Fundingmentioning

confidence: 99%

“…6 Recent animal research has noted apparently bipotential progenitor cells in rat kidneys, which may give rise to cells in both the adrenal cortex and medulla. 1 Whether a common progenitor may play a role in humans is currently unknown. It has also been postulated by some authors that adrenal neoplasms in children may arise from a cell more akin to the fetal adrenal cortex than the adult adrenal cortex; 4 it is feasible this precursor cell may have a different biological potential to that giving rise to tumours in adults.…”

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confidence: 99%

McArdle disease presenting as abnormal liver function: biochemical, anatomical and genetic characterisation in the first genetically confirmed Chinese family with a novel splicing variant

et al. 2021

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“…This gene encodes for the muscle isoform of glycogen phosphorylase (myophosphorylase), which catalyses and regulates glycogen breakdown to glucose-1-phosphate during glycogenolysis in skeletal muscle [2]. To date, more than 150 mutations have been described in the PYGM gene associated with McArdle disease, the nonsense mutation c.148C>T; p.R50* being the most prevalent in the Caucasian population [3].…”

Section: Introductionmentioning

confidence: 99%

Generation of the First Human In Vitro Model for McArdle Disease Based on iPSC Technology

Ortuño-Costela

Cerrada

Moreno-Izquierdo

et al. 2022

IJMS

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McArdle disease is a rare autosomal recessive disorder caused by mutations in the PYGM gene. This gene encodes for the skeletal muscle isoform of glycogen phosphorylase (myophosphorylase), the first enzyme in glycogenolysis. Patients with this disorder are unable to obtain energy from their glycogen stored in skeletal muscle, prompting an exercise intolerance. Currently, there is no treatment for this disease, and the lack of suitable in vitro human models has prevented the search for therapies against it. In this article, we have established the first human iPSC-based model for McArdle disease. For the generation of this model, induced pluripotent stem cells (iPSCs) from a patient with McArdle disease (harbouring the homozygous mutation c.148C>T; p.R50* in the PYGM gene) were differentiated into myogenic cells able to contract spontaneously in the presence of motor neurons and generate calcium transients, a proof of their maturity and functionality. Additionally, an isogenic skeletal muscle model of McArdle disease was created. As a proof-of-concept, we have tested in this model the rescue of PYGM expression by two different read-through compounds (PTC124 and RTC13). The developed model will be very useful as a platform for testing drugs or compounds with potential pharmacological activity.

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Clinical utility gene card for McArdle disease

Cited by 5 publications

References 24 publications

Enfermedad de McArdle en cuatro pacientes pediátricos. Algoritmo diagnóstico ante una intolerancia al ejercicio

Enfermedad de McArdle en cuatro pacientes pediátricos. Algoritmo diagnóstico ante una intolerancia al ejercicio

McArdle disease presenting as abnormal liver function: biochemical, anatomical and genetic characterisation in the first genetically confirmed Chinese family with a novel splicing variant

Generation of the First Human In Vitro Model for McArdle Disease Based on iPSC Technology

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