Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI), Molecular Diagnosis and Rare Diseases Laboratory, Department of Clinical Biochemistry, Hospital Universitario Virgen del Rocío, Seville, Spain.
Molecular Diagnosis and Rare Diseases Laboratory, Department of Clinical Biochemistry, Hospital Universitario Virgen del Rocío, Seville, Spain.
Orphanet J Rare Dis. 2021 May 21;16(1):233. doi: 10.1186/s13023-021-01864-8.
Pompe disease (PD) is an autosomal recessive metabolic disorder caused by pathogenic variants in the acid α-glucosidase gene (GAA) that produces defects in the lysosomal acid α-1,4-glucosidase. We aimed to identify genetic variations and clinical features in Spanish subjects to establish genotype-phenotype correlation.
A total of 2637 samples of patients who showed symptoms or susceptible signs of PD were enrolled in this observational study. Enzymatic activity was detected by fluorometric techniques and the genetic study was carried out using Next-Generation Sequencing.
Fourteen different variants from 17 diagnosed patients were identified, seven males and nine females with LOPD (mean age 36.07, SD 20.57, range 7-64) and a 2-day-old boy with IOPD, four genetic variants had not been described in the literature previously, including a homozygous variant. In all of them α-glucosidase activity was decreased. Muscle weakness, respiratory distress, exercise intolerance, hypotonia, dysphagia and myalgia were commonly observed in patients.
This study report four new genetic variants that contribute to the pathogenic variants spectrum of the GAA gene. We confirm that patients in Spain have a characteristic profile of a European population, with c.-32-13T>G being the most prevalent variant. Furthermore, it was confirmed that the c.236_246delCCACACAGTGC pathogenic variant in homozygosity is associated with early disease and a worse prognosis.
庞贝病（PD）是一种常染色体隐性遗传代谢疾病，由酸性α-葡萄糖苷酶基因（GAA）的致病变异引起，导致溶酶体酸性α-1,4-葡萄糖苷酶缺陷。我们旨在确定西班牙患者的遗传变异和临床特征，以建立基因型-表型相关性。
本观察性研究共纳入了 2637 例有 PD 症状或易患迹象的患者样本。通过荧光技术检测酶活性，使用下一代测序进行遗传研究。
在 17 名确诊的患者中发现了 14 种不同的变异，其中 7 名男性和 9 名女性为肢带型 PD（平均年龄 36.07，标准差 20.57，范围 7-64），还有一名 2 天大的婴儿为婴儿型 PD，其中 4 种遗传变异以前未在文献中描述，包括一种纯合变异。在所有患者中，α-葡萄糖苷酶活性均降低。肌无力、呼吸窘迫、运动不耐受、低张力、吞咽困难和肌痛是患者常见的症状。
本研究报告了 4 种新的遗传变异，它们增加了 GAA 基因的致病变异谱。我们证实，西班牙患者具有欧洲人群的特征性特征，其中最常见的变异是 c.-32-13T>G。此外，还证实了纯合 c.236_246delCCACACAGTGC 致病性变异与疾病早期和预后较差相关。
