Rapid progressive course of later-onset Pompe disease in Chinese patients

Chih Chao Yang, Yin Hsiu Chien, Ni Chung Lee, Shu Chuan Chiang, Shuan Pei Lin, Yung Ting Kuo, Shun Sheng Chen, Yuh Jyh Jong, Wuh Liang Hwu

研究成果: 雜誌貢獻文章同行評審

33 引文 斯高帕斯(Scopus)

摘要

Background: Pompe disease presents with a wide variety of phenotypes ranging from a fatal disease in infancy (the infantile-onset form) to other milder later-onset forms. Currently, the clinical manifestations in Chinese patients with later-onset Pompe disease are still not well understood. Methods: Fifteen Chinese patients who were clinically diagnosed with Pompe disease at later than one year of age at the National Taiwan University Hospital from 1993 to 2009 were included in this study. Confirmatory diagnosis included both biochemical and molecular tests. Patient outcomes after recombinant human acid α-glucosidase (GAA) therapy were also evaluated by assessing the percentage of predicted forced vital capacity in the upright position, hours of daily ventilator use, and the functional status change using Walton Gardner Medwin Scale. Results: The median age at symptom onset was 15 (12-35). years, and the median age at diagnosis was 21 (10-38). years. At the time of diagnosis or shortly after, 8 patients (53%) required mechanical ventilation. A quadriceps muscle biopsy from a 13-year-old boy already showed extensive glycogen storage and muscle fiber destruction. Mutation analysis revealed that the two dual mutations in the GAA gene c.[1935C > A; 1726G > A] (p.[D645E; G576S]) and c.[2238G > C; 1726G > A] (p.[W746C; G576S]) represented 66.5% of the mutated chromosomes. Using mutagenesis, we showed that the p.G576S pseudodeficiency mutation significantly decreased the residual enzyme activity of p.W746C. Most patients responded poorly to recombinant human GAA. Conclusions: Chinese patients with later-onset Pompe disease often showed onset of symptoms in their second decade of life with rapid disease progression, which is probably due to a specific pattern of GAA gene mutation. Therefore, early diagnosis and early treatment would be necessary to improve the prognosis of these patients.
原文英語
頁(從 - 到)284-288
頁數5
期刊Molecular Genetics and Metabolism
104
發行號3
DOIs
出版狀態已發佈 - 十一月 2011

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 遺傳學
  • 內分泌
  • 內分泌學、糖尿病和代謝

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