The emerging phenotype of long-term survivors with infantile Pompe disease

• Type of Material: Article
• Authors: Sean N. Prater, Duke University; Suhrad G. Banugaria, Duke University; Stephanie M. DeArmey, Duke University; Eleanor G. Botha, Emory University; Erin M. Stege, Children’s Hospital & Research Center Oakland; Laura E. Case, Duke University; Harrison N. Jones, Duke University; Chanika Phornphutkul, Rhode Island Hospital; Raymond Y. Wang, CHOC Childrens; Sarah P. Young, Duke University; Priya S. Kishnani, Duke University
• Language: English
• Date: 2012-09-01
• Publisher: Springer Nature [academic journals on nature.com]: Hybrid Journals - choice of CC licence
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © American College of Medical Genetics and Genomics.
• Final Published Version (URL): http://dx.doi.org/10.1038/gim.2012.44
• Title of Journal or Parent Work: Genetics in Medicine
• ISSN: 1098-3600
• Volume: 14
• Issue: 9
• Start Page: 800
• End Page: 810
• Grant/Funding Information: Supported by NIH (UL1RR024128 and TL1RR024126)
• Keywords: MANAGEMENT; CHILDREN; Genetics & Heredity; glycogen storage disease type II; enzyme replacement therapy; ENZYME REPLACEMENT THERAPY; Pompe disease; Science & Technology; CHILDHOOD; acid maltase deficiency; neuromuscular diseases; ACID ALPHA-GLUCOSIDASE; Life Sciences & Biomedicine; ARRHYTHMIAS
• Research Categories: Biology, Genetics; Health Sciences, Medicine and Surgery; Health Sciences, Pathology

Abstract

Purpose:Enzyme replacement therapy with alglucosidase alfa for infantile Pompe disease has improved survival creating new management challenges. We describe an emerging phenotype in a retrospective review of long-term survivors. Methods:Inclusion criteria included ventilator-free status and age 6 months at treatment initiation, and survival to age ≥5 years. Clinical outcome measures included invasive ventilator-free survival and parameters for cardiac, pulmonary, musculoskeletal, gross motor, and ambulatory status; growth; speech, hearing, and swallowing; and gastrointestinal and nutritional status. Results:Eleven of 17 patients met study criteria. All were cross-reactive immunologic material-positive, alive, and invasive ventilator-free at most recent assessment, with a median age of 8.0 years (range: 5.4-12.0 years). All had marked improvements in cardiac parameters. Commonly present were gross motor weakness, motor speech deficits, sensorineural and/or conductive hearing loss, osteopenia, gastroesophageal reflux, and dysphagia with aspiration risk. Seven of 11 patients were independently ambulatory and four required the use of assistive ambulatory devices. All long-term survivors had low or undetectable anti-alglucosidase alfa antibody titers. Conclusion:Long-term survivors exhibited sustained improvements in cardiac parameters and gross motor function. Residual muscle weakness, hearing loss, risk for arrhythmias, hypernasal speech, dysphagia with risk for aspiration, and osteopenia were commonly observed findings.