PMID- 31086307 OWN - NLM STAT- MEDLINE DCOM- 20200427 LR - 20240401 IS - 1530-0366 (Electronic) IS - 1098-3600 (Print) IS - 1098-3600 (Linking) VI - 21 IP - 11 DP - 2019 Nov TI - Clinical characteristics and genotypes in the ADVANCE baseline data set, a comprehensive cohort of US children and adolescents with Pompe disease. PG - 2543-2551 LID - 10.1038/s41436-019-0527-9 [doi] 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 Four patients had previously unpublished variants, and 14/83 (17%) genotyped IOPD patients were cross-reactive immunological material-negative.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. FAU - Kishnani, Priya S AU - Kishnani PS AUID- ORCID: 0000-0001-8251-909X AD - Duke University Medical Center, Durham, NC, USA. priya.kishnani@duke.edu. FAU - Gibson, James B AU - Gibson JB AUID- ORCID: 0000-0002-4052-0743 AD - Dell Children's Medical Group, Austin, TX, USA. FAU - Gambello, Michael J AU - Gambello MJ AD - Emory University School of Medicine, Atlanta, GA, USA. FAU - Hillman, Richard AU - Hillman R AD - University of Missouri Child Health, Columbia, MO, USA. FAU - Stockton, David W AU - Stockton DW AD - Children's Hospital of Michigan and Wayne State University, Detroit, MI, USA. FAU - Kronn, David AU - Kronn D AD - New York Medical College, Valhalla, NY, USA. FAU - Leslie, Nancy D AU - Leslie ND AD - Cincinnati Children's Hospital, Cincinnati, OH, USA. FAU - Pena, Loren D M AU - Pena LDM AD - Duke University Medical Center, Durham, NC, USA. AD - Cincinnati Children's Hospital, Cincinnati, OH, USA. AD - University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Tanpaiboon, Pranoot AU - Tanpaiboon P AD - Children's National Health System, Washington, DC, USA. FAU - Day, John W AU - Day JW AD - Stanford University, Stanford, CA, USA. FAU - Wang, Raymond Y AU - Wang RY AD - Children's Hospital of Orange County, Orange, CA, USA. AD - University of California-Irvine School of Medicine, Irvine, CA, USA. FAU - Goldstein, Jennifer L AU - Goldstein JL AD - Duke University Medical Center, Durham, NC, USA. FAU - An Haack, Kristina AU - An Haack K AD - Sanofi Genzyme, Cambridge, MA, USA. FAU - Sparks, Susan E AU - Sparks SE AD - Sanofi Genzyme, Cambridge, MA, USA. FAU - Zhao, Yang AU - Zhao Y AD - Sanofi Genzyme, Cambridge, MA, USA. FAU - Hahn, Si Houn AU - Hahn SH AD - Seattle Children's Hospital/University of Washington, Seattle, WA, USA. CN - Pompe ADVANCE Study Consortium LA - eng SI - ClinicalTrials.gov/NCT01526785 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190514 PL - United States TA - Genet Med JT - Genetics in medicine : official journal of the American College of Medical Genetics JID - 9815831 RN - EC 3.2.1.20 (GAA protein, human) RN - EC 3.2.1.20 (alpha-Glucosidases) SB - IM MH - Adolescent MH - Child MH - Child, Preschool MH - Cohort Studies MH - Enzyme Replacement Therapy/methods MH - Female MH - Genotype MH - Glycogen Storage Disease Type II/*epidemiology/*genetics MH - Humans MH - Infant MH - Male MH - Phenotype MH - Prospective Studies MH - United States/epidemiology MH - alpha-Glucosidases/*genetics/metabolism PMC - PMC8076035 OTO - NOTNLM OT - GAA pathogenic variants OT - alglucosidase alfa OT - glycogenosis type 2 OT - infantile-onset Pompe disease (IOPD) OT - late-onset Pompe disease (LOPD) COIS- This study was supported by Sanofi Genzyme. Authors employed by Sanofi Genzyme (K.A.H.,S.E.S.; statistician Y.Z. was employed by Sanofi Genzyme when the study was conducted) participated in study design, data collection and interpretation, provided intellectually important revisions to the manuscript, and approved the final version for publication. The authors disclose the following conflicts of interest. From Sanofi Genzyme: S.H.H.: honoraria and travel support (ADVANCE investigators' meeting); D.K.: research funding; N.D.L.: advisory board honoraria, professional writing support; L.D.M.P.: Pompe and Gaucher advisory boards and Gaucher speakers' bureau; P.T.: honoraria, travel support as clinical trial principal investigator; J.B.G.: research support, speakers' bureau; D.W.S.: Pompe Registry Advisory Board, speakers' bureau, research support, honoraria; R.W.: speaking stipend and travel support, 2014 Pompe Registry meeting; J.L.G., grants during the study; P.S.K.: Pompe and Gaucher Registry advisory boards, research support. From Actus Therapeutics: P.S.K., equity. From Alexion, Amicus, Shire, and Vertex: P.S.K., personal fees. From Baebies, Inc.: P.S.K., advisory board. From Biomarin: P.T., honoraria, travel support as clinical trial principal investigator. From New York Medical College: D.K., research funding. From Roche, Shire, and Valerion: P.S.K., grants. From Seattle Children's Hospital: S.H.H., personal fees (outside submitted work). The other authors declare no conflicts of interest. EDAT- 2019/05/16 06:00 MHDA- 2020/04/28 06:00 PMCR- 2019/05/14 CRDT- 2019/05/16 06:00 PHST- 2019/01/24 00:00 [received] PHST- 2019/04/17 00:00 [accepted] PHST- 2019/05/16 06:00 [pubmed] PHST- 2020/04/28 06:00 [medline] PHST- 2019/05/16 06:00 [entrez] PHST- 2019/05/14 00:00 [pmc-release] AID - S1098-3600(21)01059-5 [pii] AID - 527 [pii] AID - 10.1038/s41436-019-0527-9 [doi] PST - ppublish SO - Genet Med. 2019 Nov;21(11):2543-2551. doi: 10.1038/s41436-019-0527-9. Epub 2019 May 14.