3-Hydroxy-3-Methylglutaryl-CoA Lyase (HMGCL) deficiency can be a very severe disorder that typically presents with acute metabolic decompensation with features of hypoketotic hypoglycemia, hyperammonemia, and metabolic acidosis. A retrospective chart and literature review of Australian patients over their lifespan, incorporating acute and long-term dietary management, was performed. Data from 10 patients contributed to this study. The index case of this disorder was lost to follow-up, but there is 100% survival in the remainder of the cases despite several having experienced life-threatening episodes. In the acute setting, five of nine patients have used 900 mg/kg/day of sodium D,L 3-hydroxybutyrate in combination with intravenous dextrose-containing fluids (delivering glucose above estimated basal utilization requirements). All patients have been on long-term protein restriction, and those diagnosed more recently have had additional fat restriction. Most patients take L-carnitine. Three children and none of the adults take nocturnal uncooked cornstarch. Of the cohort, there were two patients that presented atypically—one with fulminant liver failure and the other with isolated developmental delay. Dietary management in patients with HMGCL deficiency is well tolerated, and rapid institution of acute supportive metabolic treatment is imperative to optimizing survival and improve outcomes in this disorder.

Skeletal muscle is a dynamic organ requiring tight regulation of energy metabolism in order to provide bursts of energy for effective function. Several inborn errors of muscle energy metabolism (IEMEM) affect skeletal muscle function and therefore the ability to initiate and sustain physical activity. Exercise testing can be valuable in supporting diagnosis, however its use remains limited due to the inconsistency in data to inform its application in IEMEM populations. While exercise testing is often used in adults with IEMEM, its use in children is far more limited. Once a physiological limitation has been identified and the aetiology defined, habitual exercise can assist with improving functional capacity, with reports supporting favourable adaptations in adult patients with IEMEM. Despite the potential benefits of structured exercise programs, data in paediatric populations remain limited. This review will focus on the utilisation and limitations of exercise testing and prescription for both adults and children, in the management of McArdle Disease, long chain fatty acid oxidation disorders, and primary mitochondrial myopathies.

Glycogen storage disease VII (GSD VII), also known as Tarui disease, is caused by a deficiency of the skeletal muscle enzyme, phosphofructokinase (PFK). Classical GSD VII is characterised by reduced exercise capacity and exercise‐induced myopathic symptoms, exacerbated with carbohydrate intake. No recommended medical or dietary therapy currently exists to improve exercise symptomology in GSD VII. An 11‐year‐old female was recommended four trial dietary therapies for 8 weeks each: (1) usual diet, (2) 150 mg/kg exogenous ketones pre‐exercise, (3) modified Atkins diet (MAD), (4) MAD and pre‐exercise ketones. Clinical assessments comprised cardiopulmonary exercise test, anthropometry, biochemical tests including creatine kinase (CK), quality of life (QoL), heart rate (HR) monitoring and subjective symptom reports. Exogenous ketones improved exercise capacity demonstrated by reduced HR for equivalent exercise workload, and participation in higher intensity exercise for longer duration. MAD improved QoL physical domain score by 29%, normalised CK and halved the number of symptoms reported per ‘physically active day’. Dissatisfaction with MAD resulted in unintentional weight loss, and a 20% reduction in QoL emotional domain score, leading to the patient declining the fourth study phase. This study is the first to demonstrate a beneficial effect of exogenous ketones, and separately, MAD, in a child with GSD VII. Exogenous ketones or MAD could be recommended under medical and dietetic supervision in GSD VII. However, consideration must be given to the potential negative impact of MAD on weight and emotional health. Further interventional studies are warranted in this condition.

Introduction: Patients with McArdle disease have reduced exercise capacity. Structured exercise programs in adults with McArdle disease can improve aerobic capacity and strength. However, structured exercise has not been evaluated in younger populations. Our aim was to determine the safety, feasibility, and acceptability of an exercise intervention in children and young adults with McArdle disease. Methods: Children and young adults aged 5–30 years with McArdle disease were recruited through metabolic clinics in New South Wales, Australia, to complete a remote, supervised 12-week exercise intervention. Pre and/or post intervention, participants completed a treadmill cardiopulmonary exercise test (CPET), strength testing, habitual physical activity monitoring, a quality-of-life questionnaire, acceptability questionnaire, muscular Near Infrared Spectroscopy (NIRS), and blood samples. Results: Five out of 10 eligible participants, with a median age of 17 years (range 13–29), were enrolled. Four met the feasibility target of 70% completed exercise sessions. Four episodes of mild rhabdomyolysis were reported during the study, but no participant required hospital admission. All participants reported they would participate in similar programs in the future. No significant changes were found in aerobic capacity, strength, habitual physical activity levels or quality of life. Trends were observed for lower perceived pain during CPET, and improved leg press. NIRS indicated a possible trend for improved muscle oxygen utilisation. Conclusion: A 12-week remotely delivered exercise intervention was found to be feasible, safe, and acceptable to children and young adults with McArdle disease. Although improvements to aerobic capacity and strength were not elicited, individual clinical benefits may have occurred. One sentence take home message: An exercise intervention in children and young adults with McArdle disease is feasible, safe, and acceptable, and may elicit individual clinical benefits.