With conventional enzyme replacement therapy (ERT), the clinical prognosis of classic Pompe disease is often unsatisfactory. About half the patients treated with ERT at the recommended dosage (20 mg/kg every other week) require ventilatory support within the first years of life. The heterogeneous response to ERT has been related to different factors, including cross-reactive immunologic material (CRIM) status and age at ERT initiation. Early treatment with a standard dosage of ERT improves clinical outcome and avoids mechanical ventilation in CRIM-positive patients detected at newborn screening, not preventing persistent hyperCKemia and muscle weakness. Later treatment with higher dosages of ERT was shown to provide similar benefits in CRIM-positive patients. Here, we report the clinical and biochemical outcomes of six patients with classic Pompe disease treated with different dosages of alglucosidase alpha at different ages. A standard dosage of ERT was employed in five patients, sharing a poor prognosis after transient clinical improvements, even in the case of early treatment (four died at 22.2±11.9 months and one survived but required tracheostomy and gastrostomy). Early higher dosage of alglucosidase alpha (40 mg/kg/week from 14 days) was administered to one CRIM-positive patient with fetal persistent bradycardia. Early higher dosage of alclucosidase alpha not only achieved normal neuromotor development but also the full correction of biochemical markers of muscle damage until 3 years of age, an unmet target with the standard dosage. Speech delay was not prevented by this approach. We suggest that early treatment with a higher dosage of ERT may further improve clinical prognosis in classic Pompe disease.

Early higher dosage of alglucosidase alpha in classic Pompe disease

Spada M.;Pagliardini V.;Ricci F.;Biamino E.;Mongini T.;Porta F.
2018-01-01

Abstract

With conventional enzyme replacement therapy (ERT), the clinical prognosis of classic Pompe disease is often unsatisfactory. About half the patients treated with ERT at the recommended dosage (20 mg/kg every other week) require ventilatory support within the first years of life. The heterogeneous response to ERT has been related to different factors, including cross-reactive immunologic material (CRIM) status and age at ERT initiation. Early treatment with a standard dosage of ERT improves clinical outcome and avoids mechanical ventilation in CRIM-positive patients detected at newborn screening, not preventing persistent hyperCKemia and muscle weakness. Later treatment with higher dosages of ERT was shown to provide similar benefits in CRIM-positive patients. Here, we report the clinical and biochemical outcomes of six patients with classic Pompe disease treated with different dosages of alglucosidase alpha at different ages. A standard dosage of ERT was employed in five patients, sharing a poor prognosis after transient clinical improvements, even in the case of early treatment (four died at 22.2±11.9 months and one survived but required tracheostomy and gastrostomy). Early higher dosage of alglucosidase alpha (40 mg/kg/week from 14 days) was administered to one CRIM-positive patient with fetal persistent bradycardia. Early higher dosage of alclucosidase alpha not only achieved normal neuromotor development but also the full correction of biochemical markers of muscle damage until 3 years of age, an unmet target with the standard dosage. Speech delay was not prevented by this approach. We suggest that early treatment with a higher dosage of ERT may further improve clinical prognosis in classic Pompe disease.
2018
31
12
1343
1347
early treatment; enzyme replacement therapy; Pompe disease; Enzyme Replacement Therapy; Female; Glycogen Storage Disease Type II; Humans; Immunologic Factors; Infant; Infant, Newborn; Male; Methotrexate; Prognosis; Rituximab; Treatment Outcome; alpha-Glucosidases
Spada M.; Pagliardini V.; Ricci F.; Biamino E.; Mongini T.; Porta F.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1786341
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