Pompe disease: pathogenesis, molecular genetics and diagnosis

Taverna, Simona; Cammarata, Giuseppe; Colomba, Paolo; Sciarrino, Serafina; Zizzo, Carmela; Francofonte, Daniele; Zora, Marco; Scalia, Simone; Brando, Chiara; Curto, Alessia Lo; Marsana, Emanuela Maria; Olivieri, Roberta; Vitale, Silvia Rita; Duro, Giovanni

doi:10.18632/aging.103794

Cited by 63 publications

(49 citation statements)

References 117 publications

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“…Axial muscles as well as respiratory muscles may also be impaired due to myopathy [4]. Patients often present clinically with back pain and exercise intolerance and dyspnea [5]. Recently, the systemic characteristics of this primary muscular disorder have been discovered: alteration of smooth muscles of the intestine and vessels, especially ectasia of vertebrobasial arteries, and the involvement of the nervous system (white matter lesions and small fiber neuropathy) widening the Pompe disease phenotype [6].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Gait and Postural Regulation in Late-Onset Pompe Disease

et al. 2020

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Pompe disease is a multisystemic disorder with the hallmark of progressive skeletal muscle weakness that often results in difficulties in walking and balance. However, detailed characterization of gait and postural regulation with this disease is lacking. The objective of this investigation was to determine if differences exist between the gait and postural regulation of LOPD patients and a matched control group. The gaits of 16 patients with LOPD were assessed using a gait analysis mobile system (RehaGait) and a dynamometric treadmill (FDM-T 1.8). The Interactive Balance System (IBS) was used to evaluate postural regulation and stability. All measures were compared to individual reference data. Demographic (age, gender), morphological (body height, body mass) and clinical data (muscle strength according to the Medical Research Council Scale (MRC Scale), as well as the 6-min walking test and a 10-m fast walk) were also recorded. Compared to individual reference data, LOPD patients presented with reduced gait velocity, cadence and time in single stand. A total of 87% of LOPD patients had abnormalities during posturographic analysis presenting with differences in postural subsystems. This study provides objective data demonstrating impaired gait and posture in LOPD patients. For follow-up analysis and as outcome measurements during medical or physiotherapeutic interventions, the findings of this investigation may be useful.

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Section: Introductionmentioning

confidence: 99%

Characterization of Gait and Postural Regulation in Late-Onset Pompe Disease

et al. 2020

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“…The search for reliable biomarkers to aid in diagnosis, progression, and response to ERT has remained elusive over the past decades. In this regard, of particular interest is the recent identification of circulating microRNAs as potential biomarkers of Pompe disease [52,53] (reviewed in [54]). These new biomarkers, in particular miR-133a, can help monitor the efficacy of the current and emerging therapies by serial sampling through liquid biopsies.…”

Section: An Expanded Set Of Clinical Characteristicsmentioning

confidence: 99%

Pompe Disease: New Developments in an Old Lysosomal Storage Disorder

Meena

Raben

2020

Biomolecules

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Pompe disease, also known as glycogen storage disease type II, is caused by the lack or deficiency of a single enzyme, lysosomal acid alpha-glucosidase, leading to severe cardiac and skeletal muscle myopathy due to progressive accumulation of glycogen. The discovery that acid alpha-glucosidase resides in the lysosome gave rise to the concept of lysosomal storage diseases, and Pompe disease became the first among many monogenic diseases caused by loss of lysosomal enzyme activities. The only disease-specific treatment available for Pompe disease patients is enzyme replacement therapy (ERT) which aims to halt the natural course of the illness. Both the success and limitations of ERT provided novel insights in the pathophysiology of the disease and motivated the scientific community to develop the next generation of therapies that have already progressed to the clinic.

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“…GAA is an alpha glucosidase, which is essential for the degradation of glycogen to glucose in lysosomes. Its deficiency leads to the glycogen accumulation in lysosomes, also known as Pompe's disease, which is an autosomal recessive disorder characterized by muscle weakness similar to NGLY1 deficiency 110,111 . Related pathways include innate immune system activation and glucose metabolism, which are also affected by NGLY1 deficiency.…”

Section: Proteins Identified In Ipscs/npcs Function In Plasma Pathwaysmentioning

confidence: 99%

Integration and comparison of multi-omics profiles of NGLY1 deficiency plasma and cellular models to identify clinically relevant molecular phenotypes

Chen

Wang

Shen

et al. 2021

Preprint

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NGLY1 (N-glycanase 1) deficiency is a rare congenital recessive disorder caused by a mutation in the NGLY1 gene, which encodes the cytosol enzyme N-glycanase 1. The NGLY1 protein catalyzes the first step in protein deglycosylation, a process prerequisite for the cytosolic degradation of misfolded glycoproteins. By performing and combining metabolomics and proteomics profiles, we showed that NGLY1 deficiency induced the activation of immune response, disturbed lipid metabolism, biogenic amine synthesis and glutathione metabolism. The discovery was further validated by profiling of patient-derived induced pluripotent stem cells (iPSCs) and differentiated neural progenitor cells (NPCs), which serve as a personalized cellular model of the disease. This study provides new insights into the NGLY1 deficiency pathology and demonstrates that the upregulation of immune response and downregulation of lipid metabolism appear to be important molecular phenotypes of NGLY1 deficiency, together with the dysregulation of amino acid metabolism, biogenic amine synthesis and diverse signaling pathways, likely causing broad downstream syndromes. Collectively, such valuable multi-omics profiles identified broad molecular associations of potential pathological mechanisms during the onset of NGLY1 deficiency and suggested potential therapeutic targets for researchers and clinicians.

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Pompe disease: pathogenesis, molecular genetics and diagnosis

Cited by 63 publications

References 117 publications

Characterization of Gait and Postural Regulation in Late-Onset Pompe Disease

Characterization of Gait and Postural Regulation in Late-Onset Pompe Disease

Pompe Disease: New Developments in an Old Lysosomal Storage Disorder

Integration and comparison of multi-omics profiles of NGLY1 deficiency plasma and cellular models to identify clinically relevant molecular phenotypes

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