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

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)284-288
Number of pages5
JournalMolecular Genetics and Metabolism
Volume104
Issue number3
DOIs
Publication statusPublished - Nov 2011

Fingerprint

Glycogen Storage Disease Type II
Mutation
Muscle
Genes
Glucosidases
Mutagenesis
Biopsy
Enzyme activity
Chromosomes
Glycogen
Vital Capacity
Quadriceps Muscle
Mechanical Ventilators
Late Onset Disorders
Taiwan
Age of Onset
Artificial Respiration
Disease Progression
Early Diagnosis
Acids

Keywords

  • Acid maltase deficiency
  • Enzyme replacement therapy
  • Genotype
  • Later-onset
  • Pompe disease

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Yang, C. C., Chien, Y. H., Lee, N. C., Chiang, S. C., Lin, S. P., Kuo, Y. T., ... Hwu, W. L. (2011). Rapid progressive course of later-onset Pompe disease in Chinese patients. Molecular Genetics and Metabolism, 104(3), 284-288. https://doi.org/10.1016/j.ymgme.2011.06.010

Rapid progressive course of later-onset Pompe disease in Chinese patients. / Yang, Chih Chao; Chien, Yin Hsiu; Lee, Ni Chung; Chiang, Shu Chuan; Lin, Shuan Pei; Kuo, Yung Ting; Chen, Shun Sheng; Jong, Yuh Jyh; Hwu, Wuh Liang.

In: Molecular Genetics and Metabolism, Vol. 104, No. 3, 11.2011, p. 284-288.

Research output: Contribution to journalArticle

Yang, CC, Chien, YH, Lee, NC, Chiang, SC, Lin, SP, Kuo, YT, Chen, SS, Jong, YJ & Hwu, WL 2011, 'Rapid progressive course of later-onset Pompe disease in Chinese patients', Molecular Genetics and Metabolism, vol. 104, no. 3, pp. 284-288. https://doi.org/10.1016/j.ymgme.2011.06.010
Yang, Chih Chao ; Chien, Yin Hsiu ; Lee, Ni Chung ; Chiang, Shu Chuan ; Lin, Shuan Pei ; Kuo, Yung Ting ; Chen, Shun Sheng ; Jong, Yuh Jyh ; Hwu, Wuh Liang. / Rapid progressive course of later-onset Pompe disease in Chinese patients. In: Molecular Genetics and Metabolism. 2011 ; Vol. 104, No. 3. pp. 284-288.
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