From exercise intolerance to functional improvement: The second wind phenomenon in the identification of McArdle disease

McArdle disease is the most common of the glycogen storage diseases. Onset of symptoms is usually in childhood with muscle pain and restricted exercise capacity. Signs and symptoms are often ignored in children or put down to 'growing pains' and thus diagnosis is often delayed. Misdiagnosis is not uncommon because several other conditions such as muscular dystrophy and muscle channelopathies can manifest with similar symptoms. A simple exercise test performed in the clinic can however help to identify patients by revealing the second wind phenomenon which is pathognomonic of the condition. Here a patient is reported illustrating the value of using a simple 12 minute walk test.RSS is funded by Ciências sem Fronteiras/CAPES Foundation. The authors would like to thank the Association for Glycogen Storage Disease (UK), the EUROMAC Registry funded by the European Union, the Muscular Dystrophy Campaign, the NHS National Specialist Commissioning Group and the Myositis Support Group for funding

Misdiagnosis is an important factor for diagnostic delay in McArdle disease

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. The frequency of misdiagnosis, duration of diagnostic delay, categories of misdiagnoses and inappropriate medical interventions were assessed in 50 genetically confirmed patients. The results demonstrated a high frequency of misdiagnosis (90%, n = 45/50) most commonly during childhood years (67%; n = 30/45) compared with teenage years and adulthood (teenage: n = 7/45; adult n = 5/45; not known n = 3/45). The correct diagnosis of McArdle disease was rarely made before adulthood (median age of diagnosis 33 years). Thirty-one patients (62%) reported having received more than one misdiagnosis; the most common were “growing pains” (40%, n = 20) and “laziness/being unfit” (46%, n = 23). A psychiatric/psychological misdiagnosis was significantly more common in females than males (females 6/20; males 1/30; p < 0.01). Of the 45 patients who were misdiagnosed, 21 (47%) received incorrect management. This study shows that most patients with McArdle disease received an incorrect explanation of their symptoms providing evidence that misdiagnosis plays an important part in delaying implementation of appropriate medical advice and management to this group of patients.The authors would like to thank Mr Andrew Wakelin for his great and inspiring work. The authors would also like to thank AGSD-UK, CAPES Foundation, Muscular Dystrophy Campaign and the Euromac Registry for their support

Is the expression of muscle glycogen phosphorylase tissue-specific? New perspectives on McArdle disease

McArdle disease is a rare glycogen storage disorder with a reported incidence of ∼1:100.000 people. It is caused by recessive mutations in the gene encoding for muscle glycogen phosphorylase (MGP), which prevents the skeletal muscle from metabolizing stored glycogen. Until very recently, MGP expression was thought to be essentially restricted to the skeletal muscle tissue. Yet, we have shown that human T lymphocytes also express MGP, which in turn plays a key role to control the migration and proliferation capacity of these cells. This finding suggests that MGP could play an important role in regulating human immune function. In addition, our group has observed previously unreported co-morbidities in patients with McArdle disease including retinopathy, thyroid disease, neurocognitive symptoms and psychiatric disorders. Here we will report on the expression levels of the three glycogen phosphorylase isoforms (brain, liver and muscle [i.e., MGP]) in human immortalized thyroid follicular epithelial (Nthy-ori-3-1) and retinal pigmented epithelium cells (ARPE-19), and in human microglia and astrocytes. We will also present data showing that the absence of expression MGP in Nthy-ori-3-1 and ARPE-19 modifies its biological functions.Sin financiación3.115 JCR (2019) Q3, 76/204 Clinical Neurology1.177 SJR (2019) Q1, 85/378 Neurology (clinical)No data IDR 2019UE