Clinical and pathophysiological clues of respiratory dysfunction in late-onset Pompe disease: New insights from a comparative study by MRI and respiratory function assessment

Gaeta, Michele; Musumeci, Olimpia; Mondello, Stefania; Ruggeri, Paolo; Montagnese, Federica; Cucinotta, Mariapaola; Vinci, Sergio Lucio; Milardi, Demetrio; Toscano, Antonio

doi:10.1016/j.nmd.2015.09.003

Cited by 40 publications

(48 citation statements)

References 23 publications

(26 reference statements)

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“…Previously, the lung area measured by MRI was shown to be linearly related to the spirometry lung volumes in healthy individuals and in patients with neuromuscular weakness 13, 22. In agreement with these studies, we found that the lung area delta representing the lung area change between maximal inspiration (total lung capacity) and the end of maximal expiration (residual volume) linearly correlated with percent predicted FVC in the DMD patients.…”

Section: Discussionsupporting

confidence: 89%

“…However, MRI offers distinct advantages as it allows analysis of the diaphragm motion at defined locations in a reproducible manner and provides assessments of the diaphragm and thoracic muscles simultaneously and independently, which is necessary in order to understand the kinetics of the respiratory pump 30. Previous studies have shown that the diaphragm is affected early in patients with Pompe disease 13, 31. We found that the diaphragm function was preserved in younger DMD patients, whereas the chest wall movement (mainly intercostal muscles) was reduced during maximal inspiration.…”

Section: Discussionmentioning

confidence: 99%

“…The difference between the two largest values of the lung area delta (the lung area at maximal inspiration minus lung area at maximal expiration) was used to investigate breathing cycle effort consistency within a subject. The diaphragm motion (DM) and the chest wall motion (CWM) were calculated on the superimposed frames of the maximal inspiration and expiration from each breathing cycle as described previously 13. The DM was measured as the area displaced by the diaphragm, defined as the area bordered by the contours of the diaphragm in maximal expiration and maximal inspiration frames on superimposed images (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Magnetic resonance imaging (MRI) has been used for detection of the diaphragm weakness in Pompe disease 12, 13. However, the temporal resolution required for the dynamic assessment often leads to poor spatial resolution and makes the image analysis challenging.…”

Section: Introductionmentioning

confidence: 99%

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Respiratory magnetic resonance imaging biomarkers in Duchenne muscular dystrophy

Mankodi

Kovacs

Norato

et al. 2017

Ann Clin Transl Neurol

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ObjectiveTo examine the diaphragm and chest wall dynamics with cine breathing magnetic resonance imaging (MRI) in ambulatory boys with Duchenne muscular dystrophy (DMD) without respiratory symptoms and controls.MethodsIn 11 DMD boys and 15 controls, cine MRI of maximal breathing was recorded for 10 sec. The lung segmentations were done by an automated pipeline based on a Holistically‐Nested Network model (HNN method). Lung areas, diaphragm, and chest wall motion were measured throughout the breathing cycle.ResultsThe HNN method reliably identified the contours of the lung and the diaphragm in every frame of each dataset (~180 frames) within seconds. The lung areas at maximal inspiration and expiration were reduced in DMD patients relative to controls (P = 0.02 and <0.01, respectively). The change in the lung area between inspiration and expiration correlated with percent predicted forced vital capacity (FVC) in patients (r s = 0.75, P = 0.03) and was not significantly different between groups. The diaphragm position, length, contractility, and motion were not significantly different between groups. Chest wall motion was reduced in patients compared to controls (P < 0.01).InterpretationCine breathing MRI allows independent and reliable assessment of the diaphragm and chest wall dynamics during the breathing cycle in DMD patients and controls. The MRI data indicate that ambulatory DMD patients breathe at lower lung volumes than controls when their FVC is in the normal range. The diaphragm moves normally, whereas chest wall motion is reduced in these boys with DMD.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Respiratory magnetic resonance imaging biomarkers in Duchenne muscular dystrophy

Mankodi

Kovacs

Norato

et al. 2017

Ann Clin Transl Neurol

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“…Therefore, early recognition of respiratory manifestations is crucial to achieve optimal therapeutic benefits for individuals with LOPD. Evaluation of respiratory involvement is based on standard pulmonary function tests, including FVC in the sitting and the supine position with measurement of the volume drop between the upright and the supine position (FVC drop), which has been suggested as a marker of diaphragmatic dysfunction [54,55] .…”

Section: Glycogen Storage Diseasesmentioning

confidence: 99%

Pulmonary Involvement in Adult Patients with Inborn Errors of Metabolism

Tran

Barbey²,

Lazor³

et al. 2017

Respiration

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Inborn errors of metabolism (IEM) are rare individually, but taken together, they affect 1 in 1,000 people. Most of the disease becomes apparent at the pediatric age; however, with the identification of late-onset forms, and with improved survival, several of these conditions may be found in adults of all ages. While the lung is not typically a primary site of clinical disease in patients with IEM, in some of them it can be a significantly affected organ with associated severe respiratory complications. Lung involvement can be a late- onset feature of a complex multisystemic disease, but sometimes it can also be the only manifestation of underlying IEM. The aim of this review is to focus on specific IEM associated with lung disease in adults and to provide the reader with an overview of the diagnostic workup, overall disease management, and specific treatments for the respiratory manifestations. Clinical suspicion, early recognition, prompt diagnosis, and appropriate care of the respiratory manifestation are crucial, as they can affect both the life expectancy and the quality of life of these patients.

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Broad variation in phenotypes for common GAA genotypes in Pompe disease

et al. 2021

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Patients with the common c.‐32‐13T > G/null GAA genotype have a broad variation in age at symptom onset, ranging from early childhood to late adulthood. Phenotypic variation for other common GAA genotypes remains largely unexplored. Here, we analyzed variation in age at symptom onset for the most common GAA genotypes using the updated and extended Pompe GAA variant database. Patients with the c.2647‐7G > A/null genotype invariably presented symptoms at adulthood, while the c.‐32‐13T > G/null, c.546G > T/null, c.1076‐22T > G/null, c.2238G > C/null, and c.2173C > T/null genotypes led to presentations from early childhood up to late adulthood. The c.1309C > T/null genotype was associated with onset at early to late childhood. Symptom onset shifted toward higher ages in homozygous patients. These findings indicate that a broad variation in symptom onset occurs for various common GAA genotypes, suggesting the presence of modifying factors. We identified three new compound heterozygous c.‐32‐13T > G/null patients who carried the genetic modifier c.510C > T and who showed symptom onset at childhood. While c.510C > T acted by lowering GAA enzyme activity, other putative genetic modifiers did not at the group level, suggesting that these act in trans on processes downstream of GAA enzyme activity.

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Clinical and pathophysiological clues of respiratory dysfunction in late-onset Pompe disease: New insights from a comparative study by MRI and respiratory function assessment

Cited by 40 publications

References 23 publications

Respiratory magnetic resonance imaging biomarkers in Duchenne muscular dystrophy

Respiratory magnetic resonance imaging biomarkers in Duchenne muscular dystrophy

Pulmonary Involvement in Adult Patients with Inborn Errors of Metabolism

Broad variation in phenotypes for common GAA genotypes in Pompe disease

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