Long-term effects of enzyme replacement therapy in an elderly cohort of late-onset Pompe disease

Maren Winkler,Christina Von Landenberg,Katharina Kuchenbecker,Jens Reimann,Cornelia Kornblum

doi:10.1016/j.nmd.2022.01.001

Maren Winkler, Christina Von Landenberg + Show 3 more

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https://doi.org/10.1016/j.nmd.2022.01.001

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Journal: Neuromuscular Disorders	Publication Date: Jan 13, 2022
Citations: 5	License type: cc-by

Affiliation: University Hospital Bonn

Abstract

Enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase (rhGAA) in late-onset Pompe disease (LOPD) shows beneficial effects in the first years often followed by a decline. We aimed to examine long-term ERT effects in an elderly LOPD cohort. Patients with age at diagnosis/start of ERT >50 years and ERT duration > seven years were included. Outcome parameters were MRC sum-score, 6 Minute Walk Test 6MWT, Quick Motor Function Test QMFT, forced vital capacity FVC sitting/supine, CK levels and rhGAA IgG antibody titers. We retrospectively analysed six patients with a median age at diagnosis/start of ERT of 63 years (range 52–69), and a median ERT duration of eight years (range 7–12). 6MWT improved in 4/6, and 2/6 each showed an improvement or stabilization in muscle strength and FVC supine. In contrast, FVC showed a decline in all patients in a sitting position, and QMFT worsened in 5/6. CK levels decreased in all patients. Antibody titers were not associated with treatment effects. Highest titers were present in best responders who were female, still ambulatory and without ventilatory support at follow-up. ERT effects were very heterogeneous and showed best results in 6MWT, followed by muscle strength in manual testing and FVC supine.

Highlights

Pompe disease is an autosomal recessive lysosomal glycogen storage disorder in which a deficiency of alpha1,4 glucosidase (GAA) leads to a preferential accumulation of glycogen in muscle cells
Our analyses focus on long-term results of Enzyme replacement therapy (ERT) in elderly Late-onset Pompe disease (LOPD) patients that were diagnosed in adulthood
Diagnosis of LOPD was based on the biochemical analysis of the alpha-1,4 glucosidase activity in skeletal muscle tissue, lymphocytes and/or dried blood spot test (DBS) as well as the presence of two heterozygous pathogenic GAA variants in all patients

Summary

Introduction

Pompe disease is an autosomal recessive lysosomal glycogen storage disorder in which a deficiency of alpha glucosidase (GAA) leads to a preferential accumulation of glycogen in muscle cells. Late-onset Pompe disease (LOPD) manifests in late childhood, adolescence or adulthood with a predominant proximal muscle weakness (limb girdle phenotype) and respiratory dysfunction. A high variety of pathogenic variants in the GAA gene have been identified in the last few years correlating partly with the clinical phenotype [1], of which the c.−32–13T>G variant is the most common one in LOPD [2,3]. The time span between first clinical symptoms and correct diagnosis is often more than six years [4]. This is devastating in the view of an available therapy

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