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Genet Med. 2019 Nov;21(11):2543-2551. doi: 10.1038/s41436-019-0527-9. Epub 2019 May 14.

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

Author information

1
Duke University Medical Center, Durham, NC, USA. priya.kishnani@duke.edu.
2
Dell Children's Medical Group, Austin, TX, USA.
3
Emory University School of Medicine, Atlanta, GA, USA.
4
University of Missouri Child Health, Columbia, MO, USA.
5
Children's Hospital of Michigan and Wayne State University, Detroit, MI, USA.
6
New York Medical College, Valhalla, NY, USA.
7
Cincinnati Children's Hospital, Cincinnati, OH, USA.
8
Duke University Medical Center, Durham, NC, USA.
9
University of Cincinnati College of Medicine, Cincinnati, OH, USA.
10
Children's National Health System, Washington, DC, USA.
11
Stanford University, Stanford, CA, USA.
12
Children's Hospital of Orange County, Orange, CA, USA.
13
University of California-Irvine School of Medicine, Irvine, CA, USA.
14
Sanofi Genzyme, Cambridge, MA, USA.
15
Seattle Children's Hospital/University of Washington, Seattle, WA, USA.

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 Four patients had previously unpublished variants, and 14/83 (17%) genotyped IOPD patients were cross-reactive immunological material-negative.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)

PMID:
31086307
DOI:
10.1038/s41436-019-0527-9

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