Rapid progressive course of later-onset Pompe disease in Chinese patients
Journal
Molecular Genetics and Metabolism
Journal Volume
104
Journal Issue
3
Pages
284-288
ISSN
1096-7206
Date Issued
2011-11
Author(s)
Chiang S.-C.
Lin S.-P.
Kuo Y.-T.
Chen S.-S.
Jong Y.-J.
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. ? 2011 Elsevier Inc.
SDGs
Other Subjects
glycogen; recombinant glucan 1,4 alpha glucosidase; adolescent; adult; article; artificial ventilation; child; Chinese; chromosome; clinical article; clinical feature; controlled study; disease course; disease duration; disease severity; enzyme activity; enzyme replacement; forced vital capacity; functional status; gene mutation; glycogen storage disease type 2; human; later onset pompe disease; muscle biopsy; muscle cell; muscle injury; nucleotide sequence; onset age; patient positioning; priority journal; prognosis; quadriceps femoris muscle; rating scale; school child; site directed mutagenesis; Taiwan; treatment outcome; treatment response; university hospital; ventilator; walton gardner medwin scale; Adolescent; Adult; alpha-Glucosidases; Asian Continental Ancestry Group; Enzyme Replacement Therapy; Glycogen Storage Disease Type II; Humans; Mutagenesis, Site-Directed; Point Mutation; Respiration, Artificial; Reverse Transcriptase Polymerase Chain Reaction; Taiwan; Treatment Outcome
Type
journal article