Late-onset Pompe disease: preliminary results of enzyme replacement therapy

Pompe disease is an orphan hereditary accumulation disease associated with a deficiency of the lysosomal enzyme alglucosidase alpha. Manifestations of the disease are associated with pathological deposition of glycogen in body tissues as a result of GAA gene mutation and subsequent reduction in the activity of the enzyme alglucosidase alpha or acid maltase. The variety of phenotypic forms and varying degrees of damage to the skeletal and respiratory muscles, cardiomyocytes and internal organs greatly complicates the diagnosis and treatment of patients with Pompe»s disease. This article describes the clinical case of late-onset Pompe disease, which was followed by a course of enzyme replacement therapy, as well as an assessment of the condition before and after treatment and preliminary results.

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Pregnancy Outcomes in Late Onset Pompe Disease and Enzyme Replacement Therapy

10.20944/preprints202007.0611.v1 ◽

2020 ◽

Author(s):

Ozlem Goker-Alpan ◽

Vellore G. Kasturi ◽

Maninder K. Sohi ◽

Renuka P. Limgala ◽

Stephanie L. Austin ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pregnancy Outcomes ◽

Pompe Disease ◽

Late Onset ◽

Small Sample Size ◽

Respiratory Muscles ◽

Small Sample ◽

Enzyme Replacement ◽

Initial Symptoms

There is limited data on pregnancy outcomes in Pompe Disease (PD) resulting from deficiency of the lysosomal enzyme acid alpha-glucosidase. Late-onset PD is characterized by progressive proximal muscle weakness and decline of respiratory function secondary to the involvement of the respiratory muscles. In a cohort of twenty-five females, the effects of both PD on the course of pregnancy and the effects of pregnancy on PD were investigated. Reproductive history, course of pregnancy, use of Enzyme replacement therapy (ERT), PD symptoms, and outcomes of each pregnancy were obtained through a questionnaire. Among 20 subjects that reported one or more pregnancies, one subject conceived while on ERT and continued therapy through two normal pregnancies with worsening of weakness during pregnancy and improvement postpartum. While fertility was not affected, pregnancy may worsen symptoms, or cause initial symptoms to arise. Complications with pregnancy or birth were not higher, except for an increase in the rate of stillbirths (3.8% compared to the national average of 0.2-0.7%). Given small sample size and possible bias of respondents being only women who have been pregnant, further data may be needed to better analyze the effects of pregnancy on PD, and the effects of ERT on pregnancy outcomes.

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New motor outcome function measures in evaluation of Late-Onset Pompe disease before and after enzyme replacement therapy

Muscle & Nerve ◽

10.1002/mus.23340 ◽

2012 ◽

Vol 45 (6) ◽

pp. 831-834 ◽

Cited By ~ 37

Author(s):

Corrado Angelini ◽

Claudio Semplicini ◽

Sabrina Ravaglia ◽

Maurizio Moggio ◽

Giacomo P. Comi ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pompe Disease ◽

Late Onset ◽

Enzyme Replacement ◽

Motor Outcome ◽

Before And After ◽

Outcome Function

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Muscle Proteomic Profile before and after Enzyme Replacement Therapy in Late-Onset Pompe Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22062850 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2850

Author(s):

Manuela Moriggi ◽

Daniele Capitanio ◽

Enrica Torretta ◽

Pietro Barbacini ◽

Cinzia Bragato ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pompe Disease ◽

Late Onset ◽

Label Free ◽

Enzyme Replacement ◽

Lysosome Biogenesis ◽

Before And After ◽

Membrane Reorganization ◽

Patient’S Outcome

Mutations in the acidic alpha-glucosidase (GAA) coding gene cause Pompe disease. Late-onset Pompe disease (LOPD) is characterized by progressive proximal and axial muscle weakness and atrophy, causing respiratory failure. Enzyme replacement therapy (ERT), based on recombinant human GAA infusions, is the only available treatment; however, the efficacy of ERT is variable. Here we address the question whether proteins at variance in LOPD muscle of patients before and after 1 year of ERT, compared withhealthy age-matched subjects (CTR), reveal a specific signature. Proteins extracted from skeletal muscle of LOPD patients and CTR were analyzed by combining gel based (two-dimensional difference gel electrophoresis) and label-free (liquid chromatography-mass spectrometry) proteomic approaches, and ingenuity pathway analysis. Upstream regulators targeting autophagy and lysosomal tethering were assessed by immunoblotting. 178 proteins were changed in abundance in LOPD patients, 47 of them recovered normal level after ERT. Defects in oxidative metabolism, muscle contractile protein regulation, cytoskeletal rearrangement, and membrane reorganization persisted. Metabolic changes, ER stress and UPR (unfolded protein response) contribute to muscle proteostasis dysregulation with active membrane remodeling (high levels of LC3BII/LC3BI) and accumulation of p62, suggesting imbalance in the autophagic process. Active lysosome biogenesis characterizes both LOPD PRE and POST, unparalleled by molecules involved in lysosome tethering (VAMP8, SNAP29, STX17, and GORASP2) and BNIP3. In conclusion this study reveals a specific signature that suggests ERT prolongation and molecular targets to ameliorate patient’s outcome.

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