Original article
A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease

https://doi.org/10.1016/j.jpeds.2005.11.033Get rights and content

Objective

To characterize the natural progression of infantile-onset Pompe disease.

Study design

Retrospective chart reviews of 168 patients with documented acid α-glucosidase deficiency and symptom onset by 12 months of age; Kaplan-Meier analysis of total and ventilator-free survival time; Cox proportional hazards regression modeling of mortality risk factors.

Results

The median age at symptom onset was 2.0 months (range 0 to 12 months), 4.7 months at diagnosis (range: prenatal to 4.2 months), 5.9 months at first ventilator support (range 0.1 to 31.1 months), and 8.7 months at death (range 0.3 to 73.4 months). Survival rates at 12 months of age were 25.7% overall and 16.9% ventilator-free; at 18 months 12.3% and 6.7%. Cardiomegaly (92%), hypotonia (88%), cardiomyopathy (88%), respiratory distress (78%), muscle weakness (63%), feeding difficulties (57%), and failure to thrive (53%) appeared after a median age of ∼4.0 months. Multiple covariate analysis confirmed that early symptom onset increased risk of early death.

Conclusion

Despite frequent therapeutic interventions, infantile-onset Pompe disease remains lethal.

Section snippets

Study Design and Patients

A questionnaire sent to physicians identified suitable study sites in Israel, Taiwan, North America, and Europe. Charts of patients with Pompe disease (with no set limit on year of birth) were screened for eligibility. Informed consent was obtained from the patient’s legal guardian if local regulatory authorities required it. Eligible cases had documented GAA enzyme deficiency or GAA gene mutation(s) in the medical record and onset of signs or symptoms by 12 months of age. Patients who had

Demographics, Family History, and Congenital Anomalies

Of 300 charts screened, 172 met all inclusion criteria; 4 of these were excluded because patients had received enzyme replacement therapy. The remaining 168 patients represented the eligible study population, coming from 32 sites in 9 countries, including the United States (n = 51; 30.4%), Taiwan (n = 46; 27.4%), Israel (n = 32; 19.0%), France (n = 21; 12.5%), the United Kingdom (n = 6; 3.6%), The Netherlands (n = 4; 2.4%), Italy (n = 4; 2.4%), Canada (n = 3; 1.8%), and Austria (n = 1, 0.6%).

Discussion

Our results document in detail the frequency and presenting age of signs and symptoms, as well as other significant clinical milestones such as first use of ventilator support and death, for infants presenting with Pompe disease within their first year of life. As expected for an autosomal recessive disorder, males and females were equally represented. Although the cases came from Israel, Taiwan, the United States, and Europe and represented predominantly 3 ethnic groups (Caucasian, Asian, and

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Supported by Genzyme Corporation.

List of members of the Infantile-onset Pompe Disease Natural History Study Group is available at www.jpeds.com.

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