Long-Term Outcome of Infantile Onset Pompe Disease Patients Treated with Enzyme Replacement Therapy - Data from a German-Austrian Cohort

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Charlotte Pfrimmer - , Justus Liebig University Giessen (Author)
  • Martin Smitka - , Department of Paediatrics, Division of Neuropediatrics (Author)
  • Nicole Muschol - , University Hospital Hamburg Eppendorf (Author)
  • Ralf A Husain - , Jena University Hospital (Author)
  • Martina Huemer - , University Children's Hospital Zurich (Author)
  • Julia B Hennermann - , University Medical Center Mainz (Author)
  • Rahel Schuler - , Justus Liebig University Giessen (Author)
  • Andreas Hahn - , Justus Liebig University Giessen (Author)

Abstract

BACKGROUND: Enzyme replacement therapy (ERT) with recombinant human alglucosidase alfa (rhGAA) was approved in Europe in 2006. Nevertheless, data on the long-term outcome of infantile onset Pompe disease (IOPD) patients at school age is still limited.

OBJECTIVE: We analyzed in detail cardiac, respiratory, motor, and cognitive function of 15 German-speaking patients aged 7 and older who started ERT at a median age of 5 months.

RESULTS: Starting dose was 20 mg/kg biweekly in 12 patients, 20 mg/kg weekly in 2, and 40 mg/kg weekly in one patient. CRIM-status was positive in 13 patients (86.7%) and negative or unknown in one patient each (6.7%). Three patients (20%) received immunomodulation. Median age at last assessment was 9.1 (7.0-19.5) years. At last follow-up 1 patient (6.7%) had mild cardiac hypertrophy, 6 (42.9%) had cardiac arrhythmias, and 7 (46.7%) required assisted ventilation. Seven patients (46.7%) achieved the ability to walk independently and 5 (33.3%) were still ambulatory at last follow-up. Six patients (40%) were able to sit without support, while the remaining 4 (26.7%) were tetraplegic. Eleven patients underwent cognitive testing (Culture Fair Intelligence Test), while 4 were unable to meet the requirements for cognitive testing. Intelligence quotients (IQs) ranged from normal (IQ 117, 102, 96, 94) in 4 patients (36.4%) to mild developmental delay (IQ 81) in one patient (9.1%) to intellectual disability (IQ 69, 63, 61, 3x <55) in 6 patients (54.5%). White matter abnormalities were present in 10 out of 12 cerebral MRIs from 7 patients.

CONCLUSION: Substantial motor, cardiac, respiratory, and cognitive deficits are frequent in IOPD long-term survivors who started ERT before 2016. The findings of this study can be valuable as comparative data when evaluating the impact of newer treatment strategies including higher enzyme dosage, immunomodulation, modified enzymes, or early start of treatment following newborn screening.

Details

Original languageEnglish
Pages (from-to)167-177
Number of pages11
JournalJournal of neuromuscular diseases
Volume11
Issue number1
Publication statusE-pub ahead of print - 27 Nov 2023
Peer-reviewedYes

External IDs

unpaywall 10.3233/jnd-230164
Mendeley ea908906-cee7-3405-8623-384d7e63a3b5
Scopus 85181852801

Keywords

Sustainable Development Goals

Keywords

  • Adolescent, Adult, Austria, Child, Enzyme Replacement Therapy/adverse effects, Europe, Glycogen Storage Disease Type II, Heart, Humans, Infant, Infant, Newborn, Young Adult