Clinical characteristics and genotypes in the ADVANCE baseline data set, a comprehensive cohort of US children and adolescents with Pompe disease

on behalf of the Pompe ADVANCE Study Consortium

Research output: Contribution to journalArticle

Abstract

Purpose: To characterize clinical characteristics and genotypes of patients in the ADVANCE study of 4000 L-scale alglucosidase alfa (NCT01526785), the largest prospective United States Pompe disease cohort to date. Methods: Patients aged ≥1 year with confirmed Pompe disease previously receiving 160 L alglucosidase alfa were eligible. GAA genotypes were determined before/at enrollment. Baseline assessments included histories/physical exams, Gross Motor Function Measure-88 (GMFM-88), pulmonary function tests, and cardiac assessments. Results: Of 113 enrollees (60 male/53 female) aged 1–18 years, 87 had infantile-onset Pompe disease (IOPD) and 26 late-onset (LOPD). One hundred eight enrollees with GAA genotypes had 215 pathogenic variants (220 including combinations): 118 missense (4 combinations), 23 splice, 35 nonsense, 34 insertions/deletions, 9 duplications (1 combination), 6 other; c.2560C>T (n = 23), c.−32-13T>G (n = 13), and c.525delT (n = 12) were most common. Four patients had previously unpublished variants, and 14/83 (17%) genotyped IOPD patients were cross-reactive immunological material–negative. All IOPD and 6/26 LOPD patients had cardiac involvement, all without c.−32−13T>G. Thirty-two (26 IOPD, 6 LOPD) were invasively ventilated. GMFM-88 total %scores (mean ± SD, median, range): overall 46.3 ± 33.0% (47.9%, 0.0–100.0%), IOPD 41.6 ± 31.64% (38.9%, 0.0–99.7%), LOPD: 61.8 ± 33.2 (70.9%, 0.0–100.0%). Conclusion: ADVANCE, a uniformly assessed cohort comprising most US children and adolescents with treated Pompe disease, expands understanding of the phenotype and observed variants in the United States.

Original languageEnglish (US)
Pages (from-to)2543-2551
Number of pages9
JournalGenetics in Medicine
Volume21
Issue number11
DOIs
StatePublished - Nov 1 2019

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Glycogen Storage Disease Type II
Genotype
Datasets
Respiratory Function Tests
History
Phenotype

Keywords

  • GAA pathogenic variants
  • alglucosidase alfa
  • glycogenosis type 2
  • infantile-onset Pompe disease (IOPD)
  • late-onset Pompe disease (LOPD)

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Clinical characteristics and genotypes in the ADVANCE baseline data set, a comprehensive cohort of US children and adolescents with Pompe disease. / on behalf of the Pompe ADVANCE Study Consortium.

In: Genetics in Medicine, Vol. 21, No. 11, 01.11.2019, p. 2543-2551.

Research output: Contribution to journalArticle

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title = "Clinical characteristics and genotypes in the ADVANCE baseline data set, a comprehensive cohort of US children and adolescents with Pompe disease",
abstract = "Purpose: To characterize clinical characteristics and genotypes of patients in the ADVANCE study of 4000 L-scale alglucosidase alfa (NCT01526785), the largest prospective United States Pompe disease cohort to date. Methods: Patients aged ≥1 year with confirmed Pompe disease previously receiving 160 L alglucosidase alfa were eligible. GAA genotypes were determined before/at enrollment. Baseline assessments included histories/physical exams, Gross Motor Function Measure-88 (GMFM-88), pulmonary function tests, and cardiac assessments. Results: Of 113 enrollees (60 male/53 female) aged 1–18 years, 87 had infantile-onset Pompe disease (IOPD) and 26 late-onset (LOPD). One hundred eight enrollees with GAA genotypes had 215 pathogenic variants (220 including combinations): 118 missense (4 combinations), 23 splice, 35 nonsense, 34 insertions/deletions, 9 duplications (1 combination), 6 other; c.2560C>T (n = 23), c.−32-13T>G (n = 13), and c.525delT (n = 12) were most common. Four patients had previously unpublished variants, and 14/83 (17{\%}) genotyped IOPD patients were cross-reactive immunological material–negative. All IOPD and 6/26 LOPD patients had cardiac involvement, all without c.−32−13T>G. Thirty-two (26 IOPD, 6 LOPD) were invasively ventilated. GMFM-88 total {\%}scores (mean ± SD, median, range): overall 46.3 ± 33.0{\%} (47.9{\%}, 0.0–100.0{\%}), IOPD 41.6 ± 31.64{\%} (38.9{\%}, 0.0–99.7{\%}), LOPD: 61.8 ± 33.2 (70.9{\%}, 0.0–100.0{\%}). Conclusion: ADVANCE, a uniformly assessed cohort comprising most US children and adolescents with treated Pompe disease, expands understanding of the phenotype and observed variants in the United States.",
keywords = "GAA pathogenic variants, alglucosidase alfa, glycogenosis type 2, infantile-onset Pompe disease (IOPD), late-onset Pompe disease (LOPD)",
author = "{on behalf of the Pompe ADVANCE Study Consortium} and Kishnani, {Priya S.} and Gibson, {James B.} and Gambello, {Michael J.} and Richard Hillman and Stockton, {David W.} and David Kronn and Leslie, {Nancy D.} and Pena, {Loren D.M.} and Pranoot Tanpaiboon and Day, {John W.} and Wang, {Raymond Y.} and Goldstein, {Jennifer L.} and {An Haack}, Kristina and Sparks, {Susan E.} and Yang Zhao and Hahn, {Si Houn}",
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AU - on behalf of the Pompe ADVANCE Study Consortium

AU - Kishnani, Priya S.

AU - Gibson, James B.

AU - Gambello, Michael J.

AU - Hillman, Richard

AU - Stockton, David W.

AU - Kronn, David

AU - Leslie, Nancy D.

AU - Pena, Loren D.M.

AU - Tanpaiboon, Pranoot

AU - Day, John W.

AU - Wang, Raymond Y.

AU - Goldstein, Jennifer L.

AU - An Haack, Kristina

AU - Sparks, Susan E.

AU - Zhao, Yang

AU - Hahn, Si Houn

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Purpose: To characterize clinical characteristics and genotypes of patients in the ADVANCE study of 4000 L-scale alglucosidase alfa (NCT01526785), the largest prospective United States Pompe disease cohort to date. Methods: Patients aged ≥1 year with confirmed Pompe disease previously receiving 160 L alglucosidase alfa were eligible. GAA genotypes were determined before/at enrollment. Baseline assessments included histories/physical exams, Gross Motor Function Measure-88 (GMFM-88), pulmonary function tests, and cardiac assessments. Results: Of 113 enrollees (60 male/53 female) aged 1–18 years, 87 had infantile-onset Pompe disease (IOPD) and 26 late-onset (LOPD). One hundred eight enrollees with GAA genotypes had 215 pathogenic variants (220 including combinations): 118 missense (4 combinations), 23 splice, 35 nonsense, 34 insertions/deletions, 9 duplications (1 combination), 6 other; c.2560C>T (n = 23), c.−32-13T>G (n = 13), and c.525delT (n = 12) were most common. Four patients had previously unpublished variants, and 14/83 (17%) genotyped IOPD patients were cross-reactive immunological material–negative. All IOPD and 6/26 LOPD patients had cardiac involvement, all without c.−32−13T>G. Thirty-two (26 IOPD, 6 LOPD) were invasively ventilated. GMFM-88 total %scores (mean ± SD, median, range): overall 46.3 ± 33.0% (47.9%, 0.0–100.0%), IOPD 41.6 ± 31.64% (38.9%, 0.0–99.7%), LOPD: 61.8 ± 33.2 (70.9%, 0.0–100.0%). Conclusion: ADVANCE, a uniformly assessed cohort comprising most US children and adolescents with treated Pompe disease, expands understanding of the phenotype and observed variants in the United States.

AB - Purpose: To characterize clinical characteristics and genotypes of patients in the ADVANCE study of 4000 L-scale alglucosidase alfa (NCT01526785), the largest prospective United States Pompe disease cohort to date. Methods: Patients aged ≥1 year with confirmed Pompe disease previously receiving 160 L alglucosidase alfa were eligible. GAA genotypes were determined before/at enrollment. Baseline assessments included histories/physical exams, Gross Motor Function Measure-88 (GMFM-88), pulmonary function tests, and cardiac assessments. Results: Of 113 enrollees (60 male/53 female) aged 1–18 years, 87 had infantile-onset Pompe disease (IOPD) and 26 late-onset (LOPD). One hundred eight enrollees with GAA genotypes had 215 pathogenic variants (220 including combinations): 118 missense (4 combinations), 23 splice, 35 nonsense, 34 insertions/deletions, 9 duplications (1 combination), 6 other; c.2560C>T (n = 23), c.−32-13T>G (n = 13), and c.525delT (n = 12) were most common. Four patients had previously unpublished variants, and 14/83 (17%) genotyped IOPD patients were cross-reactive immunological material–negative. All IOPD and 6/26 LOPD patients had cardiac involvement, all without c.−32−13T>G. Thirty-two (26 IOPD, 6 LOPD) were invasively ventilated. GMFM-88 total %scores (mean ± SD, median, range): overall 46.3 ± 33.0% (47.9%, 0.0–100.0%), IOPD 41.6 ± 31.64% (38.9%, 0.0–99.7%), LOPD: 61.8 ± 33.2 (70.9%, 0.0–100.0%). Conclusion: ADVANCE, a uniformly assessed cohort comprising most US children and adolescents with treated Pompe disease, expands understanding of the phenotype and observed variants in the United States.

KW - GAA pathogenic variants

KW - alglucosidase alfa

KW - glycogenosis type 2

KW - infantile-onset Pompe disease (IOPD)

KW - late-onset Pompe disease (LOPD)

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