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Long-Term Outcome of Infantile Onset Pompe Disease Patients Treated with Enzyme Replacement Therapy - Data from a
Charlotte Pfrimmer1, Martin Smitka2, Nicole Muschol3
1Department of Child Neurology, Justus-Liebig-University Gießen, Gießen, Germany.
Insights
Long-term enzyme replacement therapy (ERT) for infantile onset Pompe disease (IOPD) shows significant cardiac, respiratory, motor, and cognitive deficits in school-aged survivors. These findings highlight the need for improved treatment strategies for IOPD patients.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Enzyme replacement therapy (ERT) using recombinant human alglucosidase alfa (rhGAA) has been available for infantile onset Pompe disease (IOPD) since 2006.
- Long-term outcome data for IOPD patients reaching school age remains limited.
Purpose of the Study:
- To analyze the long-term cardiac, respiratory, motor, and cognitive function in German-speaking IOPD patients aged 7 and older who initiated ERT at a median age of 5 months.
- To provide valuable comparative data for evaluating new therapeutic approaches in IOPD.
Main Methods:
- Retrospective analysis of 15 German-speaking IOPD patients.
- Assessment of cardiac, respiratory, motor, and cognitive functions at a median age of 9.1 years.
- Review of ERT dosage, CRIM status, immunomodulation, and MRI findings.
Main Results:
- Significant deficits were observed: 46.7% required assisted ventilation, 42.9% had cardiac arrhythmias, and 54.5% had intellectual disability.
- Motor function varied, with 46.7% achieving independent walking, while 26.7% were tetraplegic.
- Cognitive testing revealed normal IQ in 36.4%, mild delay in 9.1%, and intellectual disability in 54.5% of patients.
Conclusions:
- Substantial motor, cardiac, respiratory, and cognitive impairments are common in long-term IOPD survivors treated with ERT initiated before 2016.
- This study provides crucial data for assessing novel treatments like higher enzyme doses, immunomodulation, or newborn screening-based early intervention.
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.
