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Prevalence of Acid alpha-Glucosidase (GAA) Pseudodefiency Allele and It’s Clinical Significance Among Patients with Cardiomyopathy

Background: Pompe disease is an autosomal recessive lysosomal storage disorder caused by deficiency of lysosomal acid alpha-glucosidase (GAA) activity, leading to the progressive accumulation of glycogen in lysosomes of the skeletal and cardiac muscles. An alpha-glucosidase (GAA) pseudodeficiency a...

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Main Authors: Han Bing, Chow, H, S,, Ling, E. Z., Chan, B. K., Chung, L. K.`, Then, I. X., Pang, H. K., Khor, S. T., Chan, C. T., Tan, K. T.`, Koh, Y. L., Cham, Asri, Said, A. Y. Y., Fong, T. K., Ong, Y. Y., Oon
Format: Article
Language:English
Published: Elsevier B.V. 2022
Subjects:
R Medicine (General)
Online Access:http://ir.unimas.my/id/eprint/41001/3/Prevalence.pdf
http://ir.unimas.my/id/eprint/41001/
https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0167527322015492?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0167527322015492%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.internationaljournalofcardiology.com%2F
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spelling my.unimas.ir.410012022-12-27T01:01:06Z http://ir.unimas.my/id/eprint/41001/ Prevalence of Acid alpha-Glucosidase (GAA) Pseudodefiency Allele and It’s Clinical Significance Among Patients with Cardiomyopathy Han Bing, Chow H, S,, Ling E. Z., Chan B. K., Chung L. K.`, Then I. X., Pang H. K., Khor S. T., Chan C. T., Tan K. T.`, Koh Y. L., Cham Asri, Said A. Y. Y., Fong T. K., Ong Y. Y., Oon R Medicine (General) Background: Pompe disease is an autosomal recessive lysosomal storage disorder caused by deficiency of lysosomal acid alpha-glucosidase (GAA) activity, leading to the progressive accumulation of glycogen in lysosomes of the skeletal and cardiac muscles. An alpha-glucosidase (GAA) pseudodeficiency allele is a change in the GAA gene sequence that results in GAA enzyme activity reduction, but does not cause Pompe disease. In Japan and Taiwan, there is high prevalence of pseudodeficiency allele (c.1725G>A and c.2065G>A) detected from their newborn screening. We observed similar prevalence of pseudodeficiency allele among our patients who had genetic test performed for suspected hereditary cardiomyopathy. Objectives: To report the prevalence of GAA pseudodeficiency allele, and to ascertain its clinical significance among patients with cardiomyopathy. Methods: The clinical data of the patients with GAA mutations were retrieved. Patients were called back for neurological examination, lung function test, measurement of creatine kinase (CK) level and dried-blood-spot for GAA enzymatic activity. Results: From January to December 2021, 33 patients underwent genetic testing. 23 out of the 33 genetic analyses included GAA mutation. 9 (39.13%) out of 23 were tested positive for pseudodeficiency allele. Their median age was 53 years (range 29-82), 44.4% were males with equal ethnic distribution (33.3% Malay, 33.3% Chinese, 33.3% Dayaks). All were heterozygous for the pseudodeficiency allele: 5 (55.6%) with c.[1726A; 2065A] allele, the other 4 (44.4%) c.2065G>A. The underlying cardiomyopathy phenotypes were hypertrophic (44.4%), transthyretin amyloid (22.2%), hypertensive (22.2%) and Fabry (11.1%). 1 patient (11.1%) with transthyretin amyloid cardiomyopathy died of advanced heart failure at age 79 years. 1 patient had mild motor weakness of the limbs attributable to thyrotoxicosis, while the other 7 patients had normal skeletal motor function. Their median predicted forced vital capacity was 87.5% (range 76-103), median CK level was 103 U/L (range 39-297) and median GAA activity was 4.8 micromol/l/h (range 3.2-9.2) [normal > 2.0]. Conclusion: The prevalence of GAA pseudodeficiency allele among patients with cardiomyopathy is 39.13%. None of the patients exhibit significant muscle weakness or respiratory insufficiency despite low normal enzymatic activity. Whether the presence of pseudodeficiency allele affects the prognosis of the underlying cardiomyopathy remains uncertain. Elsevier B.V. 2022 Article PeerReviewed text en http://ir.unimas.my/id/eprint/41001/3/Prevalence.pdf Han Bing, Chow and H, S,, Ling and E. Z., Chan and B. K., Chung and L. K.`, Then and I. X., Pang and H. K., Khor and S. T., Chan and C. T., Tan and K. T.`, Koh and Y. L., Cham and Asri, Said and A. Y. Y., Fong and T. K., Ong and Y. Y., Oon (2022) Prevalence of Acid alpha-Glucosidase (GAA) Pseudodefiency Allele and It’s Clinical Significance Among Patients with Cardiomyopathy. International Journal of Cardiology, 369 (Supp.). p. 6. ISSN 0167-5273 https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0167527322015492?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0167527322015492%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.internationaljournalofcardiology.com%2F doi:10.1016/j.ijcard.2022.10.038
institution Universiti Malaysia Sarawak
building Centre for Academic Information Services (CAIS)
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaysia Sarawak
content_source UNIMAS Institutional Repository
url_provider http://ir.unimas.my/
language English
topic R Medicine (General)
spellingShingle R Medicine (General)
Han Bing, Chow
H, S,, Ling
E. Z., Chan
B. K., Chung
L. K.`, Then
I. X., Pang
H. K., Khor
S. T., Chan
C. T., Tan
K. T.`, Koh
Y. L., Cham
Asri, Said
A. Y. Y., Fong
T. K., Ong
Y. Y., Oon
Prevalence of Acid alpha-Glucosidase (GAA) Pseudodefiency Allele and It’s Clinical Significance Among Patients with Cardiomyopathy
description Background: Pompe disease is an autosomal recessive lysosomal storage disorder caused by deficiency of lysosomal acid alpha-glucosidase (GAA) activity, leading to the progressive accumulation of glycogen in lysosomes of the skeletal and cardiac muscles. An alpha-glucosidase (GAA) pseudodeficiency allele is a change in the GAA gene sequence that results in GAA enzyme activity reduction, but does not cause Pompe disease. In Japan and Taiwan, there is high prevalence of pseudodeficiency allele (c.1725G>A and c.2065G>A) detected from their newborn screening. We observed similar prevalence of pseudodeficiency allele among our patients who had genetic test performed for suspected hereditary cardiomyopathy. Objectives: To report the prevalence of GAA pseudodeficiency allele, and to ascertain its clinical significance among patients with cardiomyopathy. Methods: The clinical data of the patients with GAA mutations were retrieved. Patients were called back for neurological examination, lung function test, measurement of creatine kinase (CK) level and dried-blood-spot for GAA enzymatic activity. Results: From January to December 2021, 33 patients underwent genetic testing. 23 out of the 33 genetic analyses included GAA mutation. 9 (39.13%) out of 23 were tested positive for pseudodeficiency allele. Their median age was 53 years (range 29-82), 44.4% were males with equal ethnic distribution (33.3% Malay, 33.3% Chinese, 33.3% Dayaks). All were heterozygous for the pseudodeficiency allele: 5 (55.6%) with c.[1726A; 2065A] allele, the other 4 (44.4%) c.2065G>A. The underlying cardiomyopathy phenotypes were hypertrophic (44.4%), transthyretin amyloid (22.2%), hypertensive (22.2%) and Fabry (11.1%). 1 patient (11.1%) with transthyretin amyloid cardiomyopathy died of advanced heart failure at age 79 years. 1 patient had mild motor weakness of the limbs attributable to thyrotoxicosis, while the other 7 patients had normal skeletal motor function. Their median predicted forced vital capacity was 87.5% (range 76-103), median CK level was 103 U/L (range 39-297) and median GAA activity was 4.8 micromol/l/h (range 3.2-9.2) [normal > 2.0]. Conclusion: The prevalence of GAA pseudodeficiency allele among patients with cardiomyopathy is 39.13%. None of the patients exhibit significant muscle weakness or respiratory insufficiency despite low normal enzymatic activity. Whether the presence of pseudodeficiency allele affects the prognosis of the underlying cardiomyopathy remains uncertain.
format Article
author Han Bing, Chow
H, S,, Ling
E. Z., Chan
B. K., Chung
L. K.`, Then
I. X., Pang
H. K., Khor
S. T., Chan
C. T., Tan
K. T.`, Koh
Y. L., Cham
Asri, Said
A. Y. Y., Fong
T. K., Ong
Y. Y., Oon
author_facet Han Bing, Chow
H, S,, Ling
E. Z., Chan
B. K., Chung
L. K.`, Then
I. X., Pang
H. K., Khor
S. T., Chan
C. T., Tan
K. T.`, Koh
Y. L., Cham
Asri, Said
A. Y. Y., Fong
T. K., Ong
Y. Y., Oon
author_sort Han Bing, Chow
title Prevalence of Acid alpha-Glucosidase (GAA) Pseudodefiency Allele and It’s Clinical Significance Among Patients with Cardiomyopathy
title_short Prevalence of Acid alpha-Glucosidase (GAA) Pseudodefiency Allele and It’s Clinical Significance Among Patients with Cardiomyopathy
title_full Prevalence of Acid alpha-Glucosidase (GAA) Pseudodefiency Allele and It’s Clinical Significance Among Patients with Cardiomyopathy
title_fullStr Prevalence of Acid alpha-Glucosidase (GAA) Pseudodefiency Allele and It’s Clinical Significance Among Patients with Cardiomyopathy
title_full_unstemmed Prevalence of Acid alpha-Glucosidase (GAA) Pseudodefiency Allele and It’s Clinical Significance Among Patients with Cardiomyopathy
title_sort prevalence of acid alpha-glucosidase (gaa) pseudodefiency allele and it’s clinical significance among patients with cardiomyopathy
publisher Elsevier B.V.
publishDate 2022
url http://ir.unimas.my/id/eprint/41001/3/Prevalence.pdf
http://ir.unimas.my/id/eprint/41001/
https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0167527322015492?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0167527322015492%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.internationaljournalofcardiology.com%2F
_version_ 1753792666138574848
score 13.211869

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