Journal Article

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

Wang, Raymond Y., Tanpaiboon, Pranoot, Sparks, Susan E., Hillman, Richard, Kronn, David, Pena, Loren D. M., Day, John W., Gibson, James B., Goldstein, Jennifer L., Stockton, David W., Gambello, Michael J., Zhao, Yang, Hahn, Si Houn, Leslie, Nancy D., Kishnani, Priya S., An Haack, Kristina

2019

Overview

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 Four patients had previously unpublished variants, and 14/83 (17%) genotyped IOPD patients were cross-reactive immunological material–negative.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

• Publisher: Nature Publishing Group US,Elsevier Limited
• Subject: Adolescent / alpha-Glucosidases - genetics / alpha-Glucosidases - metabolism / Biomedical and Life Sciences / Biomedicine / Child / Child, Preschool / Cohort Studies / Enzyme Replacement Therapy - methods / Female / Genotype / Glycogen Storage Disease Type II - epidemiology / Glycogen Storage Disease Type II - genetics / Human Genetics / Humans / Infant / Laboratory Medicine / Male / Phenotype / Prospective Studies / United States - epidemiology