Natural History of Pompe Disease

Study aim: The principal objective of the study is to find biomarkers and clinical criteria that correlate with the disease progression. Methods: Clinical information will be obtained according to a pre-defined protocol including six visits: screening visit?screening visit The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history., visit at baseline?baseline Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them., visits at 6 months, 12 months, 18 months and 24 months. At visits following tests will be performed: Respiratory assessment (including clinical assessment using the Borg scale, identification of clinical signs of alveolar hypoventilation, documentation of the daily duration on and off mechanical ventilation, spirometry, determination of lung volumes and slow vital capacity, peak cough flow, blood gazes, measurement of maximal inspiratory and expiratory pressures during the Müller maneuver, sniff nasal inspiratory pressure, mouth inspiratory pressure, twitch mouth pressure, esophageal and transdiaphragmatic pressures during voluntary respiration and following magnetic stimulation of diaphragmatic nerves, optoelectronic measurement of abdominal contribution to vital capacity, inspiratory capacity and tidal volume, measure of diaphragm mobility using ultrasound, sleep studies using polysomnography for non-ventilated patients and oximetry for patients using non-invasive mechanical ventilation, coupled with ECG?ECG A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged. recording). Motor assessment (including the MFM motor function measure scale, timed 10 meters run/walk test, timed test for standing up from sitting positions, timed test for standing up from supine position, time taken to climb 4 stairs, 6-minute walk test, three-dimensional analysis of walk, quadriceps muscle strength assessed following magnetic stimulation of femoral nerve, EMG). Assessment of body composition (including determination of lean mass, body mass index and bone mineral density by dual X-ray absorptiometry). Assessment of skeletal muscle structure using whole body magnetic resonance imaging?magnetic resonance imaging A scan that uses magnets and radio waves, not X-rays, to make detailed pictures of the inside of the body. Some implants and metal objects mean a person cannot have one.. Assessment of heart function using heart echography and ECG. Assessment of live quality (including "Rotterdam handicap scale", "Rasch-built Pompe-specific Activity (R-Pact) scale " and EQ5D-5L questionnaires). Biomaterial collection of biomarker analysis (including dosing serum CPK, GPT and GOT, GAA mutational analysis of both alleles, biobanking of serum, DNA and urine, muscle biopsy?biopsy Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope. for histological analysis, quantification of exon 2 alternative splicing and residual GAA enzyme activity, myoblast culture for quantification of alternative splicing and residual GAA enzyme activity, muscle biopsy and myoblast culture biobanking, skin biopsy for quantification of alternative splicing and residual GAA enzyme activity, fibroblast cultures for quantification of alternative splicing and residual GAA enzyme activity, biobanking of fibroblasts). In vitro treatment of myoblasts and fibroblasts with antisense oligonucleotide chemistries and quantification of restoration of normal splicing, GAA protein and GAA enzyme activity. All data collect will be introduced in a database and afterwards statistically analyzed. Expected results: To determine exact natural history of Pompe disease, to identify biomarkers useful to follow-up?follow-up The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes. the progression of Pompe disease and for quantifying therapy effects of future therapies that aim at restoring a normal splicing in patients with c.-32-13T>G mutations. Funding: This project is funded by the French Agence National de la Recherche, the French Direction Générale de l'Offre de Soins and the Acid Maltase Deficiency Association.