Pulmonary outcome measures in long‐term survivors of infantile Pompe disease on enzyme replacement therapy: A case series

Abstract

Objectives To report the respiratory function of school‐aged children with infantile Pompe disease (IPD) who started enzyme replacement therapy (ERT) in infancy and early childhood. Study Design This is a retrospective chart review of pulmonary function tests of: (a) patients with IPD 5 to 18 years of age, (b) who were not ventilator dependent, and (c) were able to perform upright and supine spirometry. Subjects were divided into a younger (5‐9 years) and older cohort (10‐18 years) for the analysis. Upright and supine forced vital capacity (FVC), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were analyzed. Results Fourteen patients, all cross‐reactive immunologic material (CRIM)‐positive, met the inclusion criteria and were included in this study. Mean upright and supine FVC were 70.3% and 64.9% predicted, respectively, in the 5‐ to 9‐year‐old cohort; and 61.5% and 52.5% predicted, respectively, in the 10‐ to 18‐year‐old group. Individual patient trends showed stability in FVC overtime in six of the 14 patients. MIPs and MEPs were consistent with inspiratory and expiratory muscle weakness in the younger and older age group but did not decline with age. Conclusion Data from this cohort of CRIM‐positive patients with IPD showed that ERT is able to maintain respiratory function in a subgroup of patients whereas others had a steady decline. There was a statistically significant decline in FVC from the upright to a supine position in both the younger and older age groups of CRIM‐positive ERT‐treated patients. Before ERT, patients with IPD were unable to maintain independent ventilation beyond the first few years of life.

Individualized Assessment of Exercise Capacity in Response to Acute and Long-Term Enzyme Replacement Therapy in Pediatric Pompe Disease

“…The possibility that increasing drug delivery by either increasing dosage or frequency of administration or by means of newer formulations might halt the progression of the disease has been suggested. Common evaluation parameters include patient-reported outcome measures (PROMs), motor function scores, pulmonary function tests and walking assessments (e.g., 6 min walking test, 6MWT) for ambulatory patients [7][8][9].…”

Lentiviral Hematopoietic Stem Cell Gene Therapy Rescues Clinical Phenotypes in a Murine Model of Pompe Disease

“…4,6,8,9 The current and only treatment option is enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA), but this is not curative and is unable to treat the nervous system due to the relative inefficiency of ERT to cross the blood-brain barrier. 6,7,[10][11][12][13] ERT can be associated with high immunogenicity, especially in patients with the most severe form and no sign of residual enzymatic activity. 14 Alternative treatment options that provide higher levels of muscle correction and can treat CNS abnormalities may offer significant benefits for affected individuals.…”

Assessment of Dysphonia in Children with Pompe Disease Using Auditory-Perceptual and Acoustic/Physiologic Methods

“…Airflow measures such as vital capacity have been linked to MPT [28,37] and recent publications have recommended the inclusion of pulmonary function tests in voice assessment [38]. Respiratory muscle weakness with early involvement of the diaphragm is a known complication of both IOPD and LOPD [1,39,40] and therefore our finding of reduced MPT in this sample of children with Pompe disease is not surprising.…”