RESEARCH PAPERS

The challenge in rare diseases is insufficient knowledge. This can lead to under-diagnosis, misdiagnosis, delays in diagnosis and inappropriate treatment. Research helps to address this. Over 200 papers are reported on in “The McArdle Disease Handbook”, and here we provide links to more selected recent research papers of interest, and landmark papers. Use the buttons on the right to jump to the two sections.

Check these two systematic reviews on aspects of the treatment of McArdle disease.

 

SELECTED PAPERS

These papers are listed in reverse date order and we have allocated keywords to help you search for what you want.

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CLINICAL PRACTICE GIUDELINES

CLINICAL PRACTICE GUIDELINES FOR GLYCOGEN STORAGE DISEASE V & VII (MCARDLE DISEASE AND TARUI DISEASE) FROM AN INTERNATIONAL STUDY GROUP

Neuromuscular Disorders, December 2021

The Guidelines, developed by an international team of clinicians and researchers led by IamGSD, are published in Neuromuscular Disorders, the official journal of the World Muscle Society. A significant landmark in the progress of the understanding and treatment of McArdle’s and Tarui disease. Available to all free of charge under Open Access.

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NUTRITION

NO EFFECT OF ORAL KETONE ESTER SUPPLEMENTATION ON EXERCISE CAPACITY IN PATIENTS WITH MCARDLE DISEASE

Neuromuscular Disorders, October 2021

A randomized placebo-controlled cross-over study. An increase in KB oxidation by oral KE supplementation cannot fully compensate for the KB-induced inhibition of lipolysis and glycolysis, explaining why the drink failed to improve exercise capacity. Thus, oral KE supplementation alone cannot be recommended as treatment option for patients with GSDV.

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COHORT • COMORBIDITIES

NATURAL HISTORY OF MCARDLE DISEASE: A SINGLE CENTRE STUDY OF A COHORT OF 220 PATIENTS

Neuromuscular Disorders, October 2021

We extensively describe phenotypic and genotypic features of a large cohort of people with McArdle disease, all attending the Highly Specialized McArdle Disease and Related Disorders service at the National Hospital for Neurology and Neurosurgery, London.

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PAO • NUTRITION

INTERNATIONAL PATIENT GROUP HARNESSES SOCIAL MEDIA TO HELP INFORM RESEARCH: USE OF A LOW CARBOHYDRATE KETOGENIC DIET

Current Opinion in Endocrinology, Diabetes and Obesity, October 2021

To highlight the benefits of a partnership between patient advocacy organizations (PAO) and clinical researchers in order to clinically study the prior anecdotal patient experience of utilizing a low-carbohydrate ketogenic diet (LCKD) to manage McArdle disease.

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MUSCLE WASTING

MCARDLE DISEASE PATIENTS HAVE INCREASED FAT REPLACEMENT OF PARASPINAL MUSCLES: EUROPEAN MULTICENTER STUDY

Neuromuscular Disorders, July 2021

The aim of this study was to quantify fatty replacement of paraspinal and extremity muscles by magnetic resonance imaging (MRI) in a European cohort of patients with McArdle disease. The findings show that patients exhibit significant muscle fatty replacement in paraspinal muscles. This can have important implications for future management of patients.

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NUTRITION

THE POTENTIAL OF A KETOGENIC DIET TO MINIMIZE EFFECTS OF THE METABOLIC FAULT IN GSD V AND VII

Current Opinion in Endocrinology, Diabetes and Obesity, October 2020

To explore the potential of a low carbohydrate ketogenic diet (LCKD) to counter physical activity intolerance, pain and muscle damage for glycogen storage disease (GSD) V and VII, and highlight the realistic possibility that nutrition could be key.

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EXERCISE • METABOLISM

INVESTIGATION OF THE EXISTENCE AND CHARACTERISTICS OF A “THIRD WIND” PHENOMENON IN MCARDLE DISEASE

Neuromuscular Disorders, October 2019

Fourteen participants walked at a self-selected pace on a motorised treadmill for 151 min (2 hr 31 min). Six were genetically confirmed GSDV (McArdle group) and eight were pathology free individuals (Control group). Expired gas samples were collected at selected timepoints throughout and calculations of fat and carbohydrate use were made using RER. In prolonged exercise up to 121 minutes those with McArdle disease appear to use different metabolism to those without pathology. Between minute 121 and 151 the non-linear rise in fat use in the McArdle group does suggest that there is a change at c2hr that could substantiate the suggestion of a ‘Third Wind’.

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PHARMACOLOGICAL

THE EFFECT OF TRIHEPTANOIN IN ADULTS WITH MCARDLE DISEASE

Annals of Clinical and Translational Neurol​ogy, September 2019

In other metabolic diseases studies of Triheptanoin diet have shown that Triheptanoin increased metabolism of both fat and sugar, and had a positive effect on physical performance and reduced the level of symptoms. However, in McArdle’s the interpretation of the findings was negative: “Despite increased resting plasma malate with Triheptanoin, the increase was insufficient to generate a normal TCA turnover during exercise and the treatment has no effect on exercise capacity or oxidative metabolism in patients with McArdle disease.”

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MANAGEMENT

CENTRE OF EXPERTISE: COMPREHENSIVE CARE FOR PATIENTS WITH MCARDLE DISEASE

Journal Rare Disorders: Diagnosis & Therapy, 2018

The limited prevalence of this disease translates into a global challenge of limited specialist care for patients with McArdle disease. A Centre of Expertise (CoE) represents the most expansive platform to provide patients with McArdle disease current best practice that encompass thorough assessments, accurate diagnostic methods, relevant information and guidance, multidisciplinary support and an ongoing interface between primary and specialist care.

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DIAGNOSIS

MISDIAGNOSIS AND DIAGNOSTIC DELAY IN MCARDLE DISEASE

Neuromuscular Disorders, 2017

Diagnosis of McArdle disease is frequently delayed by many years following the first presentation of symptoms to a health professional. The aim of this study was to investigate the importance of misdiagnosis in delaying diagnosis of McArdle disease.

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COHORT • GENETICS

GENOTYPIC AND PHENOTYPIC FEATURES OF ALL SPANISH PATIENTS WITH MCARDLE DISEASE: A 2016 UPDATE

34th FIMS World Sports Medicine Congress, 2017

The aim of this study was to update the main genotype and phenotype characteristics, as well as potential associations within/between them, of all Spanish individuals who are currently diagnosed with McArdle disease.

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NUTRITION • EXERCISE

CAN A LOW-CARBOHYDRATE DIET IMPROVE EXERCISE TOLERANCE IN MCARDLE DISEASE

Journal Rare Disorders: Diagnosis and Therapy, 2017

A carbohydrate-restricted diet may provide patients with McArdle disease with a consistent energy substrate for working muscles, thereby reducing the risk of muscle damage and threat of renal failure. Further research on the use of a LCKD in McArdle disease is warranted.

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GENETICS • METABOLISM

HIGHER OXIDATIVE STRESS IN SKELETAL MUSCLE OF MCARDLE DISEASE PATIENTS

Molecular Genetics and Metabolism Reports, 2017

This study examines oxidative stress in McArdle patients and suggests future studies should evaluate a potential role for oxidative stress contributing to acute pathology (rhabdomyolysis) and possibly later onset fixed myopathy.

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EXERCISE • NUTRITION

EXERCISE AND PRE-EXERCISE NUTRITION AS TREATMENT FOR MCARDLE DISEASE

Medicine and Science in Sports and Exercise, 2016

Review of the role of exercise in McArdle disease with the aim to better inform health-care professionals and thus better serve the interests of patients. Recommendations for regular exercise together with preexercise nutrition in children and adult patients are also provided along with examples of exercise practice and its benefits.

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NUTRITION • METABOLISM

DIFFERENTIAL GLUCOSE METABOLISM IN MICE AND HUMANS AFFECTED BY MCARDLE DISEASE

APS Physiological Genomics, August 2016

Carbohydrate metabolism in terms of glucose transport, glycolysis, glycogen synthesis, and glycogen breakdown in proximal and distal hind limb muscles from adult homozygous “McArdle” (PYGM p.R50X/p.R50X) and wild-type (wt/wt) mice were studied. In addition, this study compares potential changes in glucose homeostasis.

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GENETICS • EXERCISE

GENES AND EXERCISE INTOLERANCE: INSIGHTS FROM MCARDLE DISEASE

Physiological Genomics, 2016

Regular physical activity attenuates the clinical severity of McArdle disease. This is quite remarkable for a monogenic disorder that consistently leads to the same metabolic defect at the muscle tissue level, that is, complete inability to use muscle glycogen stores. Further knowledge of this disorder would help patients and enhance understanding of exercise metabolism as well as exercise genomics. Indeed, McArdle disease is a paradigm of human physical activity intolerance and PYGM genotyping should be included in the genetic analyses that might be applied in the coming personalized exercise medicine as well as in future research on genetics and exercise-related phenotypes.

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PSYCHOLOGY • RARE DISEASE

WALKING WITH MCARDLE DISEASE: ALIENATION AND SOLIDARITY IN A RARE DISEASE JOURNEY

Rare Diseases and Orphan Drugs, 2015

First-hand written narratives are a particularly valuable resource for understanding the lived experience (as opposed to the medical facts) of disease. A person with McArdle disease, a very rare disorder of muscle, wrote an account of her 32-day trek across the countryside and mountains of Wales. Her narrative is in the form of a daily diary detailing the events of each day’s walking, together with her thoughts and feelings. I present an inductive and semantic analysis of this text. Prominent themes include the alienation of having a rare disease, but also a strong sense of solidarity in the journey, and the normal pleasures and tribulations of walking the British countryside.

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EXERCISE

CARDIORESPIRATORY FITNESS, PHYSICAL ACTIVITY, AND QUALITY OF LIFE IN PATIENTS WITH MCARDLE DISEASE

Medicine & Science In Sports & Exercise, 2014

All patients showed a CRF below their age-/sex-matched normality value and scored clinically lower in the physical component summary and in most SF-36 domains compared with the Spanish general population. Patients showed a consistent link between higher physical HRQoL scores and higher CRF. Patients fulfilling leisure time PA recommendations showed higher CRF and physical HRQoL scores than those not meeting guideline recommendations. According to normative data for healthy subjects, CRF and physical HRQoL are severely impaired in adult patients with McArdle disease.

 

LANDMARK PAPERS

There are a number of papers which deserve recognition as landmarks in the understanding of McArdle disease and other muscle GSDs. We are going to list them for you here.