Related Experiment Video
Updated: May 31, 2026
In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease
Published on: December 20, 2017
Rapid progressive course of later-onset Pompe disease in Chinese patients
Chih-Chao Yang1, Yin-Hsiu Chien, Ni-Chung Lee
1Department of Neurology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Insights
Later-onset Pompe disease in Chinese patients often begins in adolescence with rapid progression, linked to specific GAA gene mutations. Early diagnosis and treatment are crucial for improving outcomes in this rare genetic disorder.
Area of Science:
- Rare genetic disorders
- Neuromuscular diseases
- Metabolic myopathies
Background:
- Pompe disease exhibits diverse phenotypes, from infantile to later-onset forms.
- Clinical manifestations of later-onset Pompe disease in Chinese populations remain poorly understood.
Purpose of the Study:
- To characterize the clinical features, genetic mutations, and treatment responses in Chinese patients with later-onset Pompe disease.
- To investigate the impact of specific GAA gene mutations on disease progression and enzyme activity.
Main Methods:
- Retrospective analysis of 15 Chinese patients diagnosed with later-onset Pompe disease.
- Confirmatory diagnosis using biochemical and molecular tests.
- Evaluation of treatment outcomes with recombinant human acid alpha-glucosidase (GAA) therapy, assessing pulmonary function and functional status.
Main Results:
- Median onset age was 15 years, median diagnosis age was 21 years; 53% required mechanical ventilation at diagnosis.
- Two common GAA gene mutations, c.[1935C>A; 1726G>A] and c.[2238G>C; 1726G>A], accounted for 66.5% of mutated alleles.
- The p.G576S mutation significantly reduced enzyme activity in conjunction with p.W746C; most patients showed poor response to recombinant human GAA therapy.
Conclusions:
- Later-onset Pompe disease in Chinese patients presents with early adolescent onset and rapid progression, likely due to specific GAA gene mutations.
- Early diagnosis and intervention are essential for improving the prognosis of Chinese patients with later-onset Pompe disease.
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.
More Related Videos
Related Concept Videos
01:21Huntington Disease l: Introduction
01:24Parkinson Disease l: Introduction
01:24Parkinson Disease ll: Pathophysiology
01:22Lysosomal Hydrolases
01:15Parkinson's Disease: Overview
01:20COPD: Pathogenesis and Clinical Features
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...