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Observational Study
. 2023 Sep;30(9):2828-2837.
doi: 10.1111/ene.15894. Epub 2023 Jun 10.

Long-term follow-up of 64 children with classical infantile-onset Pompe disease since 2004: A French real-life observational study

Marine Tardieu  1 , Céline Cudejko  2 , Aline Cano  2 , Célia Hoebeke  2 , Delphine Bernoux  2 , Violette Goetz  1 , Samia Pichard  3 , Anaïs Brassier  3 , Manuel Schiff  3 , François Feillet  4 , Paul Rollier  5 , Karine Mention  6 , Dries Dobbelaere  6 , Alain Fouilhoux  7 , Caroline Espil-Taris  8 , Didier Eyer  9 , Frédéric Huet  10 , Ulrike Walther-Louvier  11 , Magalie Barth  12 , Laurent Chevret  13 , Alice Kuster  14 , Jérémie Lefranc  15 , Julien Neveu  16 , Gaele Pitelet  16 , Juliette Ropars  17 , François Rivier  11   18 , Agathe Roubertie  19 , Guy Touati  20 , Catherine Vanhulle  21 , Emilie Tardieu  22 , Catherine Caillaud  23 , Roseline Froissart  24 , Murielle Champeaux  2 , François Labarthe  1   25 , Brigitte Chabrol  2
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Free article
Observational Study

Long-term follow-up of 64 children with classical infantile-onset Pompe disease since 2004: A French real-life observational study

Marine Tardieu et al. Eur J Neurol. 2023 Sep.
Free article

Abstract

Background: Classical infantile-onset Pompe disease (IOPD) is the most severe form of Pompe disease. Enzyme replacement therapy (ERT) has significantly increased survival but only a few studies have reported long-term outcomes.

Methods: We retrospectively analyzed the outcomes of classical IOPD patients diagnosed in France between 2004 and 2020.

Results: Sixty-four patients were identified. At diagnosis (median age 4 months) all patients had cardiomyopathy and most had severe hypotonia (57 of 62 patients, 92%). ERT was initiated in 50 (78%) patients and stopped later due to being ineffective in 10 (21%). Thirty-seven (58%) patients died during follow-up, including all untreated and discontinued ERT patients, and 13 additional patients. Mortality was higher during the first 3 years of life and after the age of 12 years. Persistence of cardiomyopathy during follow-up and/or the presence of heart failure were highly associated with an increased risk of death. In contrast, cross-reactive immunologic material (CRIM)-negative status (n = 16, 26%) was unrelated to increased mortality, presumably because immunomodulation protocols prevent the emergence of high antibody titers to ERT. Besides survival, decreased ERT efficacy appeared after the age of 6 years, with a progressive decline in motor and pulmonary functions for most survivors.

Conclusions: This study reports the long-term follow-up of one of the largest cohorts of classical IOPD patients and demonstrates high long-term mortality and morbidity rates with a secondary decline in muscular and respiratory functions. This decreased efficacy seems to be multifactorial, highlighting the importance of developing new therapeutic approaches targeting various aspects of pathogenesis.

Keywords: enzyme replacement therapy; immunomodulation; infantile-onset Pompe disease; long-term outcomes.

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References

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