Although patients with childhood-onset Pompe disease are likely to develop anti-recombinant human alpha-glucosidase (rhGAA) antibodies following enzyme replacement therapy (ERT), clinical outcomes remained unaffected even in the few patients with high antibody titer levels, according to results from a study published in the Orphanet Journal of Rare Diseases.

A research team led by Nadine A.M.E. van der Beek from Erasmus University Medical Center in Rotterdam, Netherlands measured anti-rhGAA antibody titer levels using enzyme-linked immunosorbent assays at multiple times in 22 children with Pompe disease (aged 1.1 to 16.4 years) receiving alglucosidase alfa.

Specialized physical therapists and practitioners assessed functional outcomes every 3 to 6 months between June 1999 and January 2019. Clinical outcome measures included manual muscle testing using Medical Research Council scoring, the Quick Motor Function Test, upright forced vital capacity, and the Bayley Scales of Infant Development-2 for patients aged under 2 years. The investigators also recorded any infusion-associated reactions (IARs) during ERT.

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Twenty children (91%) developed anti-rhGAA antibodies above baseline. Based on the highest titer level observed during the research period, the researchers subdivided the children into 3 groups: 2 with low titers (<1:1250), 15 with intermediate titers (1:1250-1:31,250), and 5 with high titers (≥1:31,250).

Most children (82%) developed peak anti-rhGAA antibody titers within the first year of receiving ERT followed by a typical course of declining and stabilizing titers. Only 1 patient in the high titer group exhibited consistently high titer levels after baseline, and 4 children experienced IARs, 2 of whom demonstrated high anti-rhGAA antibody titers.

These 2 children in the high titer group accounted for 86% of recorded IARs, none of which were severe enough to discontinue ERT. While high titers of neutralizing antibodies may predispose children with Pompe disease to IARs during ERT, these high titers did not negatively influence clinical outcome measures.

“Neutralizing antibodies do not play a major role in the efficacy of ERT in childhood onset Pompe disease patients,” the researchers concluded.


van Kooten HA, Ditters IAM, Hoogeveen-Westerveld M, et al. Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease. Orphanet J Rare Dis. 2022;17(1):31. doi:10.1186/s13023-022-02175-2