Toward an Understanding of GSD5 (McArdle disease): How Do Individuals Learn to Live with the Metabolic Defect in Daily Life.

BACKGROUND: Glycogen storage disease type 5 (GSD) is an autosomal recessive inherited metabolic myopathy caused by a deficiency of the enzyme muscle glycogen phosphorylase. Individuals with GSD5 experience physical activity intolerance. OBJECTIVE: This patient-led study aimed to capture the daily life experiences of GSD5, with a focus on adapting to and coping with their physical activity intolerance. METHODS: An online survey was composed in close collaboration with patient organizations. It consisted of customized and validated questionnaires on demographics, general health and comorbidities, physical activity, psychosocial well-being and functioning, pain, fatigue and adapting to and coping with GSD5. RESULTS: One hundred sixty-two participants (16 countries) participated. The majority, n = 86 (69%) were from the Netherlands, USA or UK. We observed a high rate of misdiagnosis prior to GSD5 diagnosis (49%), surprisingly a relatively high proportion had not been diagnosed by DNA testing which is the gold standard. Being diagnosed had a strong impact on emotional status, daily life activities and important life choices. A large proportion had not received any rehabilitation (41%) nor medical treatment (57%) before diagnosis. Engagement in vigorous and moderate physical activity was reduced. Health related quality of life was low, most likely related to low physical health. The median Fatigue Severity Score was 4.3, indicating moderate to severe fatigue. Participants themselves had found various ways to adapt to and cope with their disability. The adaptations concerned all aspect of their life, including household chores, social and physical activities, and work. In addition to lack of support, participants reported limited availability of information sources. CONCLUSION: Participants have provided guidance for newly diagnosed people, including the advice to accept one's limited abilities and maintain an active lifestyle. We conclude that adequate counseling on ways of adapting and coping is expected to increase both health-related quality of life and physical activity.

Patient-Reported Experiences with a Low-Carbohydrate Ketogenic Diet: An International Survey in Patients with McArdle Disease.

The low-carbohydrate ketogenic diet (LCKD) has attracted increased attention in recent years as a potential treatment option for individuals with McArdle disease (glycogen storage disease type V), and despite the absence of strong scientific evidence of the LCKD's benefits, increased numbers of individuals with McArdle disease have tried a LCKD. The objective of this study was to collect patient-reported experiences with a LCKD. We aimed to estimate the immediate prevalence of individuals that had tried a LCKD in an international McArdle disease cohort, and we aimed to report on the patient-reported experiences with the diet, both positive and negative. A total of 183 responses were collected from individuals with McArdle disease from 18 countries. We found that one-third of the cohort had tried a LCKD, and almost 90% experienced some degree of positive effect, with the most prominent effects on McArdle disease-related core symptoms (e.g., activity intolerance, muscle pain, and muscle fatigue). Adverse effects were rare and generally rated as mild to moderate. These patient-reported findings underline the need for randomized clinical trials to decisively determine if a LCKD is a suitable nutritional strategy for patients with McArdle disease. The results from this study can prompt and contribute to the design of such a clinical trial.

International patient group harnesses social media to help inform rare disease research: use of a low carbohydrate ketogenic diet in McArdle disease.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: The bedside-to-bench and back again method of translational research is well suited to explore anecdotal patient experiences, particularly for rare diseases. In McArdle disease, patients have explored the use of a LCKD to address the ubiquitous occurrence of physical activity intolerance and minimize associated adverse events. The International Association for Muscle Glycogen Storage Disease harnessed the power of social media to better understand this patient-centric finding and has subsequently partnered with clinical researchers to convey patient-centered priorities for research. From this partnership, a series of clinical and survey studies have been initiated. SUMMARY: Collaboration between PAOs and clinical researchers has the potential to foster patient empowerment, advance anecdotal experiences into scientific hypotheses, and ultimately guide the development of management guidelines that reflect the patient perspective.

The potential of a ketogenic diet to minimize effects of the metabolic fault in glycogen storage disease V and VII.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: Carbohydrate (CHO) ingestion during physical activity in GSDV and a LCKD for GSDVII is common. For the latter, a long-term study demonstrated improvement in physiological markers while on a LCKD. This included improvement in aerobic power and activity tolerance. In GSDV, preliminary research on a LCKD suggest a diet of 75% fat, 15% protein, 10% CHO, is best for improved function and compliance. Ketones provide immediate fuel for acute physical activity, and have an epigenetic role, improving ketone and lipid use. Evidence from elite athletes found a LCKD can increase fat oxidation and is optimal at 70% VO2max. This suggests the need to also improve conditioning via exercise to maximize the benefit of a LCKD. SUMMARY: A high CHO diet in GSDV and VII comes with a restricted physical activity capacity alongside significant pain, muscle damage and risk of renal failure. Mounting evidence suggests a LCKD is efficacious for both disorders providing an immediate fuel source which may negate the need for a 'warm-up' prior to every activity and restore 'normal' function.