title: Childhood Pompe disease: clinical spectrum and genotype in 31 patients.
abstract: As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all patients younger than 18 years, who had been evaluated at the Pompe Center in Rotterdam, the Netherlands, between 1975 and 2012, excluding those with the classic-infantile form. None were treated with enzyme replacement therapy at the time of evaluation. We collected information on first symptoms, diagnosis, use of a wheelchair and/or respirator, and enzyme and mutation analysis and assessed muscle strength, pulmonary function, and cardiac parameters.
  
  
  
  Thirty-one patients participated. Median age at symptom onset was 2.6 years (range 0.5-13y) and at diagnosis 4.0 years. Most first problems were delayed motor development and problems related to limb-girdle weakness. Fatigue, persistent diarrhea and problems in raising the head in supine position were other first complaints. Ten patients were asymptomatic at time of diagnosis. Five of them developed symptoms before inclusion in this study. Over 50 % of all patients had low or absent reflexes, a myopathic face, and scoliosis; 29 % were underweight. Muscle strength of the neck flexors, hip extensors, hip flexors, and shoulder abductors were most frequently reduced. Pulmonary function was decreased in over 48 % of the patients; 2 patients had cardiac hypertrophy. Patients with mutations other than the c.-32-13T > G were overall more severely affected, while 18 out of the 21 patients (86 %) with the c.-32-13T > G/'null' genotype were male.
  
  
  
  Our study shows that Pompe disease can present with severe mobility and respiratory problems during childhood. Pompe disease should be considered in the differential diagnosis of children with less familiar signs such as disproportional weakness of the neck flexors, unexplained fatigue, persistent diarrhea and unexplained high CK/ASAT/ALAT. Disease presentation appears to be different from adult patients. The majority of affected children with GAA genotype c.-32-13T > G/'null' appeared to be male.
authors.affiliation: Pompe Center and Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Room Sb-1629, P.O. BOX 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: C I
authors.initials: CI
authors.lastname: van Capelle
authors.affiliation: Pompe Center and Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Room Sb-1629, P.O. BOX 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: van der Meijden
authors.affiliation: Pompe Center and Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Room Sb-1629, P.O. BOX 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: J M P
authors.initials: JM
authors.lastname: van den Hout
authors.affiliation: Centre for Metabolic Disease, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Jaeken
authors.affiliation: Department of Pediatrics, Hospital "Dritter Orden", Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Baethmann
authors.affiliation: NIHR Biomedical Research Centre, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Voit
authors.affiliation: Pompe Center and Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Room Sb-1629, P.O. BOX 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Kroos
authors.affiliation: Division of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: T G J
authors.initials: TG
authors.lastname: Derks
authors.affiliation: Department of Pediatrics and Laboratory Genetic Metabolic Diseases, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: M E
authors.initials: ME
authors.lastname: Rubio-Gozalbo
authors.affiliation: Department of Pediatric Neurology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Willemsen
authors.affiliation: Charles Dent Metabolic Unit at University College London Hospitals, London, UK.
authors.forename: R H
authors.initials: RH
authors.lastname: Lachmann
authors.affiliation: Villa Metabolica, Centre for Pediatric and Adolescent Medicine, Mainz, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Mengel
authors.affiliation: Department of Enzymology and Cellular Function, Institute of Child Health, Aghia Sophia Children's Hospital, Athens, Greece.
authors.forename: H
authors.initials: H
authors.lastname: Michelakakis
authors.affiliation: Department of Pediatrics, Division of Pediatric Respiratory Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: de Jongste
authors.affiliation: Pompe Center and Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Room Sb-1629, P.O. BOX 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: A J J
authors.initials: AJ
authors.lastname: Reuser
authors.affiliation: Pompe Center and Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Room Sb-1629, P.O. BOX 2060, 3000 CB, Rotterdam, The Netherlands. a.vanderploeg@erasmusmc.nl.
authors.forename: A T
authors.initials: AT
authors.lastname: van der Ploeg
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003937:Diagnosis, Differential; D005260:Female; D005838:Genotype; D006009:Glycogen Storage Disease Type II / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007223:Infant; D008297:Male; D009043:Motor Activity; D009154:Mutation; D000520:alpha-Glucosidases / Q000235:genetics / Q000378:metabolism
chemical_list: C509951:GAA protein, human; D000520:alpha-Glucosidases
keywords: Childhood; Clinical spectrum; Genotype; Natural course; Pompe disease