Universidad Pablo de Olavide, Sevilla, Spain.
Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
BMC Genomics. 2017 Nov 14;18(Suppl 8):819. doi: 10.1186/s12864-017-4188-2.
We recently described the genotype/phenotype features of all Spanish patients diagnosed with McArdle disease as of January 2011 (n = 239, prevalence of ~1/167,000) (J Neurol Neurosurg Psychiatry 2012;83:322-8). Several caveats were however identified suggesting that the prevalence of the disease is actually higher.
We have now updated main genotype/phenotype data, as well as potential associations within/between them, of all Spanish individuals currently diagnosed with McArdle disease (December 2016).
Ninety-four new patients (all Caucasian) have been diagnosed, yielding a prevalence of ~1/139,543 individuals. Around 55% of the mutated alleles have the commonest PYGM pathogenic mutation p.R50X, whereas p.W798R and p.G205S account for 10 and 9% of the allelic variants, respectively. Seven new mutations were identified: p.H35R, p.R70C, p.R94Q, p.L132WfsX163, p.Q176P, p.R576Q, and c.244-3_244-2CA. Almost all patients show exercise intolerance, the second wind phenomenon and high serum creatine kinase activity. There is, however, heterogeneity in clinical severity, with 8% of patients being asymptomatic during normal daily life, and 21% showing limitations during daily activities and fixed muscle weakness. A major remaining challenge is one of diagnosis, which is often delayed until the third decade of life in 72% of new patients despite the vast majority (86%) reporting symptoms before 20 years. An important development is the growing proportion of those reporting a 4-year improvement in disease severity (now 34%) and following an active lifestyle (50%). Physically active patients are more likely to report an improvement after a 4-year period in the clinical course of the disease than their inactive peers (odds ratio: 13.98; 95% confidence interval: 5.6, 34.9; p < 0.001). Peak oxygen uptake is also higher in the former (20.7 ± 6.0 vs. 16.8 ± 5.3 mL/kg/min, p = 0.0013). Finally, there is no association between PYGM genotype and phenotype manifestation of the disease.
The reported prevalence of McArdle disease grows exponentially despite frequent, long delays in genetic diagnosis, suggesting that many patients remain undiagnosed. Until a genetic cure is available (which is not predicted in the near future), current epidemiologic data support that adoption of an active lifestyle is the best medicine for these patients.
我们最近描述了截至 2011 年 1 月所有被诊断为 McArdle 病的西班牙患者的基因型/表型特征（n=239，患病率约为 1/167000）（J Neurol Neurosurg Psychiatry 2012；83:322-8）。然而，我们发现了一些需要注意的问题，表明该疾病的实际患病率更高。
我们现在更新了所有西班牙 McArdle 病患者的主要基因型/表型数据，以及它们之间的潜在关联（截至 2016 年 12 月）。
我们诊断出 94 名新患者（均为白种人），患病率约为 1/139543 人。约 55%的突变等位基因携带最常见的 PYGM 致病性突变 p.R50X，而 p.W798R 和 p.G205S 分别占等位基因突变的 10%和 9%。我们发现了 7 种新突变：p.H35R、p.R70C、p.R94Q、p.L132WfsX163、p.Q176P、p.R576Q 和 c.244-3_244-2CA。几乎所有患者都表现出运动不耐受、第二风现象和高血清肌酸激酶活性。然而，临床严重程度存在异质性，8%的患者在日常生活中无症状，21%的患者在日常活动和固定肌肉无力方面存在限制。一个主要的挑战仍然是诊断，尽管绝大多数（86%）患者在 20 岁之前就有症状，但仍有 72%的新患者直到 30 岁才得到确诊。一个重要的发展是，越来越多的患者报告疾病严重程度在 4 年内得到改善（现在为 34%），并保持积极的生活方式（50%）。积极运动的患者比不积极运动的患者在疾病病程的 4 年后更有可能报告病情改善（优势比：13.98；95%置信区间：5.6，34.9；p<0.001）。前者的峰值摄氧量也更高（20.7±6.0 vs. 16.8±5.3 mL/kg/min，p=0.0013）。最后，PYGM 基因型与疾病表型表现之间没有关联。
尽管基因诊断经常出现长期延误，但 McArdle 病的报告患病率呈指数级增长，表明许多患者仍未得到诊断。在获得基因治疗（预计在不久的将来不会出现）之前，目前的流行病学数据支持积极的生活方式是这些患者的最佳治疗方法。
