Clinical and Laboratory Findings on Glycogen Storage Disease Type V: Re-sults from a Retrospective Observational Study in a Tertiary Hospital

Title:Clinical and Laboratory Findings on Glycogen Storage Disease Type V: Re-sults from a Retrospective Observational Study in a Tertiary Hospital

Volume: 24 Issue: 16

Author(s): A. Pereira*, J. Diogo da Silva, A. Rita Soares, A. Guimas, S. Rocha, M. Cardoso, C. Garrido, C. Azevedo Soares, I. Nunes, A. Maria Fortuna, D. Quelhas, S. Figueiroa, R. Ribeiro, M. Santos, E. Martins and N. Tkachenko

Affiliation:

• Pediatric Neurology, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário de Santo António, Porto, Portugal
• Pediatrics, Hospital de Braga, Braga, Portugal

Abstract: Introduction: Glycogen storage disease type V (GSDV, MIM #232600) is an autosomal re-cessive metabolic myopathy caused by pathogenic variants in the PYGM gene. The characteristic symp-toms of exercise intolerance, myalgia, and cramps, which improve after a few minutes of rest, are fre-quently unrecognized in affected children. When there is clinical suspicion, the initial approach with a forearm exercise test has diagnostic value by detecting low post-exercise plasma lactate-to-ammonia ratio values. The diagnostic algorithm is followed by genetic testing if the results suggest myophosphor-ylase deficiency.

Methods: This was a retrospective observational study conducted based on reviewing medical records of patients with GSDV in a tertiary hospital. We assessed demographic variables, including the timing of onset and diagnosis, relevant clinical characteristics, and whether genetic testing was performed, in-cluding its results.

Results/Case Report: Our goal was to review the GSDV cases in our center to assess our cohort's diag-nostic timing and clinical and genetic characteristics. We identified 28 patients from 24 families, three with consanguinity. The mean age at the time of the study was 43 years. While most (26/28; 93%) re-called their first symptoms in childhood/adolescence, only 25% (7/28) were diagnosed then. All patients had exercise intolerance and CK elevation, while about half reported the second wind phenomenon. Ge-netic testing was performed in 22 patients, revealing biallelic PYGM variants (9 homozygous, 13 com-pound heterozygous) as the most common (p.R50*).

Conclusion: GSDV is rare and presents in the pediatric age, with subtle manifestations often underesti-mated for decades. A late diagnosis may negatively impact the psychosocial development of affected children. It is essential to recognize some unique features that facilitate diagnosis: history of exercise intolerance, the second wind sign, and high resting serum CK levels. Identifying the disease-causing variants in PYGM is currently the gold standard for diagnosis as it is less invasive than performing a muscle biopsy, and may promptly diagnose the condition and avoid wrongful labelling of patients.

Cite this article as:

Pereira A.*, Diogo da Silva J., Soares A. Rita, Guimas A., Rocha S., Cardoso M., Garrido C., Azevedo Soares C., Nunes I., Maria Fortuna A., Quelhas D., Figueiroa S., Ribeiro R., Santos M., Martins E. and Tkachenko N., Clinical and Laboratory Findings on Glycogen Storage Disease Type V: Re-sults from a Retrospective Observational Study in a Tertiary Hospital, Endocrine, Metabolic & Immune Disorders - Drug Targets 2024; 24 (16) . https://dx.doi.org/10.2174/1871530323666230914122936