Molecular Diagnosis of Pompe Disease in the Genomic Era: Correlation with Acid Alpha-Glucosidase Activity in Dried Blood Spots

Thuriot, Fanny; Gravel, Elaine; Hodson, Katherine; Ganopolsky, Jorge G.; Rakić, Bojana; Waters, Paula J.; Gravel, Serge; Levesque, Sébastien

doi:10.3390/jcm10173868

Cited by 3 publications

(3 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The two remaining low values represented only one pathogenic variant. 10,11 In our study, the mean age at diagnosis was 2 months for the infantile form and 15 years for the late-onset form. This was similar to most of the earlier studies.…”

Section: Discussionmentioning

confidence: 56%

Screening for Pompe Disease in High-Risk Pediatric Patients: Experience from a Tertiary Care Center in Rajasthan

Nagpal¹,

Goyal

Mathur

et al. 2023

Journal of Pediatric Neurology

View full text Add to dashboard Cite

A high index of suspicion is required to diagnose rare genetic disorders, such as Pompe disease, with common clinical manifestations in children. There is a need to sensitize physicians regarding cues to early screening and diagnosis of such patients. Minimal epidemiological data are available on Pompe disease in India. The aim of this study was to determine the prevalence of Pompe disease in high-risk pediatric populations and determine the appropriateness of screening dried blood spot (DBS) tests to facilitate the diagnosis of Pompe disease. We screened pediatric patients presented with (1) unexplained hypotonia, respiratory distress, cardiomyopathy, and elevated liver function tests; and (2) unexplained limb girdle muscle weakness through a DBS test for enzyme assay. Those patients found positive underwent acid alpha-glucosidase mutational analysis. This prospective cross-sectional study was conducted in 45 suspected patients after approval from the institutional ethical committee. Of the 45 suspected patients, 9 (20%) were found to be positive by DBS test. Out of these nine tested, four (44.4%) were positive, two (22.2%) were negative, and three (33.3%) could not be tested for mutation analysis. The prevalence of genetically confirmed Pompe disease in high-risk populations was 8.8%. The results of this study show that clinical suspicion and DBS filter paper test facilitate early diagnosis and management, thereby improving the quality of life in patients. DBS test acts as a robust, rapid first-tier screening test for Pompe disease.

show abstract

Section: Discussionmentioning

confidence: 56%

Screening for Pompe Disease in High-Risk Pediatric Patients: Experience from a Tertiary Care Center in Rajasthan

Nagpal¹,

Goyal

Mathur

et al. 2023

Journal of Pediatric Neurology

View full text Add to dashboard Cite

show abstract

“…Also, incorrect blood spotting and the combination of humidity and heat caused by insufficient drying or inappropriate shipping can interfere with enzyme stability and, consequently, the assessment of GAA levels [ 98 ]. Rarely, positive DBS with no pathogenic variant may also be related to pseudodeficiency alleles [ 40 , 99 , 100 ]. As a screening test for LOPD, quantification of PAS-positive lymphocytes in peripheral blood has recently demonstrated its usefulness [ 101 ].…”

Section: Clinical Assessment and Diagnostic Toolsmentioning

confidence: 99%

A Comprehensive Update on Late-Onset Pompe Disease

Labella,

Cotti Piccinelli,

Risi

et al. 2023

Biomolecules

View full text Add to dashboard Cite

Pompe disease (PD) is an autosomal recessive disorder caused by mutations in the GAA gene that lead to a deficiency in the acid alpha-glucosidase enzyme. Two clinical presentations are usually considered, named infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD), which differ in age of onset, organ involvement, and severity of disease. Assessment of acid alpha-glucosidase activity on a dried blood spot is the first-line screening test, which needs to be confirmed by genetic analysis in case of suspected deficiency. LOPD is a multi-system disease, thus requiring a multidisciplinary approach for efficacious management. Enzyme replacement therapy (ERT), which was introduced over 15 years ago, changes the natural progression of the disease. However, it has limitations, including a reduction in efficacy over time and heterogeneous therapeutic responses among patients. Novel therapeutic approaches, such as gene therapy, are currently under study. We provide a comprehensive review of diagnostic advances in LOPD and a critical discussion about the advantages and limitations of current and future treatments.

show abstract

“…Moreover, some genetic variants lead to pseudodeficiency, which is characterized by patients having low enzymatic activity in blood but not producing any muscle damage. 15 …”

Section: Introduction To Pompe Diseasementioning

confidence: 99%

Therapeutic Options for the Management of Pompe Disease: Current Challenges and Clinical Evidence in Therapeutics and Clinical Risk Management

Bolano-Diaz¹,

Díaz‐Manera²

2022

TCRM

View full text Add to dashboard Cite

Pompe disease is a genetic disorder produced by mutations in the GAA gene leading to absence or reduced expression of acid alpha-glucosidase, an enzyme that metabolizes the breakdown of glycogen into glucose. There are two main phenotypes, the infantile consisting of early onset severe weakness and cardiomyopathy, and the adult which is characterized by slowly progressive skeletal and respiratory muscle weakness. Enzymatic replacement therapy (ERT) has been available for Pompe disease for more than 15 years. Although the treatment has improved many aspects of the disease, such as prolonged survival through improved cardiomyopathy and acquisition of motor milestones in infants and slower progression rate in adults, ERT is far from being a cure as both infantile and adult patients continue to progress. This fact has prompted the development of improved or new enzymes and other treatments such as gene therapy or substrate reduction strategies. Here, we review the data obtained from randomized clinical trials but also from open-label studies published so far that have assessed the advantages and limitations of this therapy. Moreover, we also review the new therapeutic strategies that are under development and provide our opinion on which are the unmet needs for patients with this disease.

show abstract

Molecular Diagnosis of Pompe Disease in the Genomic Era: Correlation with Acid Alpha-Glucosidase Activity in Dried Blood Spots

Cited by 3 publications

References 38 publications

Screening for Pompe Disease in High-Risk Pediatric Patients: Experience from a Tertiary Care Center in Rajasthan

Screening for Pompe Disease in High-Risk Pediatric Patients: Experience from a Tertiary Care Center in Rajasthan

A Comprehensive Update on Late-Onset Pompe Disease

Therapeutic Options for the Management of Pompe Disease: Current Challenges and Clinical Evidence in Therapeutics and Clinical Risk Management

Contact Info

Product

Resources

About