title: The emerging phenotype of long-term survivors with infantile Pompe disease.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Sean N
authors.initials: SN
authors.lastname: Prater
authors.forename: Suhrad G
authors.initials: SG
authors.lastname: Banugaria
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: DeArmey
authors.forename: Eleanor G
authors.initials: EG
authors.lastname: Botha
authors.forename: Erin M
authors.initials: EM
authors.lastname: Stege
authors.forename: Laura E
authors.initials: LE
authors.lastname: Case
authors.forename: Harrison N
authors.initials: HN
authors.lastname: Jones
authors.forename: Chanika
authors.initials: C
authors.lastname: Phornphutkul
authors.forename: Raymond Y
authors.initials: RY
authors.lastname: Wang
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Young
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
mesh_terms: D001323:Autoantibodies / Q000097:blood; D001851:Bone Diseases, Metabolic / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003679:Deglutition; D003680:Deglutition Disorders / Q000473:pathology; D056947:Enzyme Replacement Therapy; D005260:Female; D005764:Gastroesophageal Reflux / Q000473:pathology; D006009:Glycogen Storage Disease Type II / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D034381:Hearing Loss / Q000473:pathology; D006801:Humans; D008297:Male; D018908:Muscle Weakness / Q000473:pathology; D010641:Phenotype; D012189:Retrospective Studies; D013064:Speech Disorders / Q000473:pathology; D017741:Survivors; D016896:Treatment Outcome; D000520:alpha-Glucosidases / Q000008:administration & dosage* / Q000097:blood
chemical_list: D001323:Autoantibodies; C509951:GAA protein, human; D000520:alpha-Glucosidases