Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy

Orphanet J Rare Dis. 2018 Feb 8;13(1):32. doi: 10.1186/s13023-018-0771-0.


Background: Enzyme replacement therapy (ERT) has deeply modified the clinical history of Infantile Onset Pompe Disease (IOPD). However, its long-term effectiveness is still not completely defined. Available data shows a close relationship between clinical outcome and patients' cross-reactive immunological status (CRIM), being CRIM-negative status a negative prognostic factor. At the same time limited data are available on the long-term treatment in CRIM-positive infants.

Methods: A retrospective multicentre observational study was designed to analyse the long-term effectiveness of ERT in IOPD. Thirteen Italian centres spread throughout the country were involved and a cohort of 28 patients (15 females, 13 males, born in the period: February 2002-January 2013) was enrolled. IOPD diagnosis was based on clinical symptoms, enzymatic and molecular analysis. All patients received ERT within the first year of life. Clinical, laboratory, and functional data (motor, cardiac and respiratory) were collected and followed for a median period of 71 months (5 years 11 months).

Results: Median age at onset, diagnosis and start of ERT were 2, 3 and 4 months, respectively. CRIM status was available for 24/28 patients: 17/24 (71%) were CRIM-positive. Nineteen patients (67%) survived > 2 years: 4 were CRIM-negative, 14 CRIM-positive and one unknown. Six patients (5 CRIM-positive and one unknown) never needed ventilation support (21,4%) and seven (6 CRIM-positive and one unknown: 25%) developed independent ambulation although one subsequently lost this function. Brain imaging study was performed in 6 patients and showed peri-ventricular white matter abnormalities in all of them. Clinical follow-up confirmed the better prognosis for CRIM-positive patients, though a slow, progressive worsening of motor and/or respiratory functions was detected in 8 patients.

Conclusions: These data are the result of the longest independent retrospective study on ERT in IOPD reported so far outside clinical trials. The data obtained confirmed the better outcome of the CRIM-positive patients but at the same time, showed the inability of the current therapeutic approach to reverse or stabilize the disease progression. The results also evidenced the involvement of central nervous system in Pompe disease. To better understand the disease clinical history and to improve treatment efficacy larger multicentre studies are needed as well as the development of new therapeutic approaches.

Keywords: Alglucosidase alpha; ERT; Infantile onset Pompe disease; Recombinant human GAA; rhGAA.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Child, Preschool
  • Cohort Studies
  • Female
  • Glycogen Storage Disease Type II / drug therapy*
  • Humans
  • Infant
  • Italy
  • Male
  • Recombinant Proteins
  • Retrospective Studies
  • alpha-Glucosidases / administration & dosage
  • alpha-Glucosidases / therapeutic use*


  • Recombinant Proteins
  • alpha-Glucosidases