Challenges in diagnosis and treatment of late-onset Pompe disease

Desnuelle, Claude; Salviati, Leonardo

doi:10.1097/wco.0b013e32834a1e00

Cited by 13 publications

(15 citation statements)

References 61 publications

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“…Even in LOPD, treatment can be beneficial, aiding in prevention of damage to muscle and organs. Furthermore, without NBS, misdiagnosis and diagnostic odysseys are common, particularly in LOPD (Desnuelle and Salviati 2011;Hobson-Webb and Kishnani 2012;Dasouki et al 2014;Lisi et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Newborn screening for Pompe disease: impact on families

Pruniski

Lisi

Ali

2018

J of Inher Metab Disea

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Pompe disease (PD) is an autosomal recessive lysosomal storage disorder causing progressive glycogen accumulation in muscles, with variability in age of onset and severity. For infantile-onset PD (IOPD), initiation of early treatment can be life-saving; however, current newborn screening (NBS) technology cannot distinguish IOPD from late-onset PD (LOPD) without clinical workup. Therefore, families of LOPD infants diagnosed by NBS may now spend years or even decades aware of their illness before symptoms appear, creating a pre-symptomatic awareness phase with which the medical community has little experience. The present study examines the effects of receiving a positive NBS result for PD on families. In-depth qualitative interviews were conducted with mothers of nine children (three IOPD and six LOPD) diagnosed via NBS, exploring their experiences, understanding of PD, how they are coping, and what impact diagnosis is having on family life. Interviews were coded using MaxQDA v.12 and analyzed for thematic trends. While overall opinion of NBS was favorable, it is clear many of the concerns anticipated by HCPs, patients, and families regarding NBS for late-onset LSDs are being realized to varying degrees; LOPD families are becoming patients-in-waiting. Increased fear/anxiety and living with uncertainty (regarding diagnosis, their children's future, and when to start treatment) were predominant themes, with all families voicing considerable emotional reactions and varied social and healthcare support concerns. Coping strategies and psychosocial challenges are interpreted using Rolland & Williams' Family Systems Genetic Illness model. Recommendations for improvement in delivery of service, as well as families' advice for future parents and HCPs, are discussed.

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Section: Introductionmentioning

confidence: 99%

Newborn screening for Pompe disease: impact on families

Pruniski

Lisi

Ali

2018

J of Inher Metab Disea

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“…In Pompe disease, for example, failure to digest glycogen leads to progressive accumulation of glycogen in the lysosomes and the cytoplasm. The accumulations results in lysosomal expansion in many tissues, and leads to cardiac failure and skeletal myopathy [182]. In Tay–Sachs disease (GM2 gangliosidosis), dysfunctional β-hexosaminidase A, a lysosomal enzyme to degrade ganglioside GM2, results in accumulation of GM2 in expanded lysosomal structures in the brain, and ultimately leads to neuronal death.…”

Section: Membrane Trafficking and Maintenance: What Keeps The Healthymentioning

confidence: 99%

Membrane trafficking in neuronal maintenance and degeneration

Wang

Chan

Cherry

et al. 2012

Cell. Mol. Life Sci.

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Defects in membrane trafficking and degradation are hallmarks of most, and maybe all, neurodegenerative disorders. Such defects typically result in the accumulation of undegraded proteins due to aberrant endosomal sorting, lysosomal degradation, or autophagy. The genetic or environmental cause of a specific disease may directly affect these membrane trafficking processes. Alternatively, changes in intracellular sorting and degradation can occur as cellular responses of degenerating neurons to unrelated primary defects such as insoluble protein aggregates or other neurotoxic insults. Importantly, altered membrane trafficking may contribute to the pathogenesis or indeed protect the neuron. The observation of dramatic changes to membrane trafficking thus comes with the challenging need to distinguish pathological from protective alterations. Here, we will review our current knowledge about the protective and destructive roles of membrane trafficking in neuronal maintenance and degeneration. In particular, we will first focus on the question of what type of membrane trafficking keeps healthy neurons alive in the first place. Next, we will discuss what alterations of membrane trafficking are known to occur in Alzheimer’s disease and other tauopathies, Parkinson’s disease, polyQ diseases, peripheral neuropathies, and lysosomal storage disorders. Combining the maintenance and degeneration viewpoints may yield insight into how to distinguish when membrane trafficking functions protectively or contributes to degeneration.

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“…In addition, we analyzed all five lysosomal enzyme activities in 825 normal non-affected newborns ( Table 5). All patients presented clinically with late onset phenotypes [1,11] except Pompe Patient 3, Niemann Pick Patient I and MPS I Patient 1 ( Table 4). All affected patients could be differentiated from normal newborns in this first pilot study by using the 0.5th percentile of lysosomal enzyme activities from normal newborns as a preliminary cut-off value.…”

Section: Clinical Evaluationmentioning

confidence: 99%

Short-incubation mass spectrometry assay for lysosomal storage disorders in newborn and high-risk population screening

Mechtler

Metz

Müller

et al. 2012

Journal of Chromatography B

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The interest in early detection strategies for lysosomal storage disorders (LSDs) in newborns and high-risk population has increased in the last years due to the availability of novel treatment strategies coupled with the development of diagnostic techniques. We report the development of a short-incubation mass spectrometry-based protocol that allows the detection of Gaucher, Niemann-Pick A/B, Pompe, Fabry and mucopolysaccharidosis type I disease within 4h including sample preparation from dried blood spots. Optimized sample handling without the need of time-consuming offline preparations, such as liquid-liquid and solid-phase extraction, allows the simultaneous quantification of five lysosomal enzyme activities using a cassette of substrates and deuterated internal standards. Applying incubation times of 3h revealed in intra-day CV% values ranging from 4% to 11% for all five enzyme activities, respectively. In a first clinical evaluation, we tested 825 unaffected newborns and 16 patients with LSDs using a multiplexed, turbulent flow chromatography-ultra high performance liquid chromatography-tandem mass spectrometer assay. All affected patients were identified accurately and could be differentiated from non-affected newborns. In comparison to previously published two-day assays, which included an overnight incubation, this protocol enabled the detection of lysosomal enzyme activities from sample to first result within half a day.

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Challenges in diagnosis and treatment of late-onset Pompe disease

Cited by 13 publications

References 61 publications

Newborn screening for Pompe disease: impact on families

Newborn screening for Pompe disease: impact on families

Membrane trafficking in neuronal maintenance and degeneration

Short-incubation mass spectrometry assay for lysosomal storage disorders in newborn and high-risk population screening

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