Reference values for the 12 minute walk test in McArdle patients.

The maximum distance achieved on a modified 12 min walk test (12MWT) is a well-established measure in McArdle disease glycogen storage disease type V (GSDV). Age, height, body mass and gender are known predictors of walking distance in other patient groups. Reference values to correct for these predictors are necessary for comparisons between individuals. To date, there has not been a systematic investigation of these predictors in the 12MWT in GSDV. This study explores the contribution of these predictors on distance achieved in GSDV. Data, included maximum distance walked, age, gender, height and body mass, was collected from 103 GSDV patients who underwent 12MWT between 2011 and 2017. Analysis showed a significant correlation between distance achieved and height, age, body mass and gender. Multiple linear regression analysis revealed a model accounting for 29.7% of variance (R = 0.545, R2 0.297, adjusted R2 0.269). Gender was not significant after height, age and body mass were entered into the regression analysis. This is the first study to report the contribution of non-disease related factors on distance achieved on the 12MWT in the GSDV population. The reference values generated will allow for improved monitoring and assessment of GSDV patients in clinical and research settings.

The need for biochemical testing in beta-enolase deficiency in the genomic era.

Glycogen storage disease type XIII (GSDXIII) is a very rare inherited metabolic myopathy characterized by autosomal-recessive mutations in the ENO3 gene resulting in muscle ß-enolase deficiency, an enzymatic defect of the distal part of glycolysis. Enzyme kinetic studies of two patients presenting with exertion intolerance and recurrent rhabdomyolysis are reported. Next generation sequencing confirmed patient 1 was homozygous for p.E187K in ENO3, while patient 2 was homozygous for p.C357Y. ENO3 variants pathogenicity was confirmed by functional studies in skeletal muscle. p.E187K caused extremely low total enolase activity. p.C357Y was associated with a higher level of residual activity but kinetic studies showed a lower maximum work rate (V max). This study illustrates that GSDXIII may be caused by either null mutations leading to ß-enolase deficiency or by mutations that alter the enzyme's kinetic profile. This study highlights the importance of carrying out functional studies as part of the diagnostic process following the identification of variants with next generation sequencing.

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.

McArdle Disease Misdiagnosed as Meningitis.

BACKGROUND McArdle disease is a glycogen storage disorder mainly characterized by exercise intolerance. Prolonged muscle contracture is also a feature of this condition and may lead to rhabdomyolysis (RM), which is a serious event characterized by acute skeletal muscle damage.  CASE REPORT A 44-year-old female patient presented with an acute contracture of the posterior neck muscles, causing severe nuchal rigidity. The contracture was induced during a dental extraction as she held her mouth open for a prolonged period, with her neck in a rigid position. She presented with severe pain in her ear and head, as well as fever, vomiting, and confusion. Based on her symptoms, she was initially misdiagnosed with bacterial meningitis and experienced an acute allergic reaction to the systemic penicillin she was subsequently administered. Lumbar puncture results were normal. High serum creatine kinase (CK) levels, recurrent exercise-related muscle symptoms, and a previous history of recurrent myoglobinuria raised the suspicion of an underlying neuromuscular condition. McArdle disease was confirmed by muscle biopsy and a genetic test, which revealed that the patient was homozygous for the R50X mutation in the PYGM gene. CONCLUSIONS This case illustrates that even seemingly innocuous movements, if rapid isotonic or prolonged isometric in nature, can elicit a muscle contracture in McArdle disease patients. Here, we highlight the need for careful management in this patient population even during routine healthcare procedures. The allergic reaction to antibiotics emphasises that misdiagnoses may result in iatrogenic harm.

Family-supportive organization perceptions: validation of an abbreviated measure and theory extension.

Although the concept of family-supportive organization perceptions has been well received in the literature, the actual construct has been relatively understudied. In the present study, we accomplish two goals. First using confirmatory factor analysis, we report on the validation of an abbreviated six-item measure of family-supportive organization perceptions that demonstrates limited measurement error. Second, we link role theory, social support resource theory, and the direct effects model of social support, to suggest that the way in which family-supportive organization perceptions affect work-family conflict is via experiences of domain overload. Contrary to the direct effects model of social support, family-supportive organization perceptions do not differentially impact work and family overload. Consistent with social support resource theory though, the effects of family-supportive organization perceptions on work-to-family and family to-work conflict are fully mediated via work and family overload (respectively). Avenues for future research incorporating family-supportive organization perceptions are also considered.