Abstract
Background
Glycogen storage disease type V (GSDV) is an autosomal recessive metabolic condition caused by pathogenic PYGM variants. This is an underdiagnosed condition as it presents with exercise intolerance in children. We reviewed the GSDV cases of a tertiary hospital center to assess diagnostic timing/accuracy, as well as potential clinical/analytical predictors of such factors.
Methods
We retrospectively reviewed all GSDV cases with follow-up in both Pediatric and Adult Metabolic Diseases consultations. We included 28 cases and assessed their hospital record for clinical information.
Results
Over 90% of our cases had late diagnoses, with more than 50% being diagnosed in adulthood despite symptom onset in preschool (very late diagnosis). Diagnostic age was lower in patients exhibiting myoglobinuria. Interestingly, patients with a positive family history of GSDV had similar rates of very late diagnoses, likely since the index case was already detected very late in life. Finally, we observe that the R50* variant is associated with increased myoglobinuria and CK elevation, in a dosage-dependent manner.
Conclusion
We concluded that GSDV is severely underdiagnosed, and that some clinical and analytical aspects of the condition can be more indicative of this diagnosis. Furthermore, we propose for the first time a genotype–phenotype correlation in GSDV.
Impact
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GSDV is a pediatric-onset metabolic disorder that is mostly diagnosed late in the adult age and commonly misdiagnosed.
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We observed the first genotype–phenotype correlation in GSDV, regarding the common R50* variant.
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Awareness of GSDV for pediatricians and the overall medical community is vital.
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Data availability
All data regarding this work are present in the manuscript and its online materials.
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Funding
Funding was provided by UMIB—Unidade Multidisciplinar de Investigação Biomédica, ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal, and by ITR—Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal, both supported by FCT—Fundação para a Ciência e a Tecnologia in the frameworks of UIDP/00215/2020; LA/P/0064/2020.
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All authors met the Pediatric Research authorship requirements. J.D.D.S., A.P. and N.T. conceived and designed the study. J.D.D.S., A.P., A.R.S., A.G., S.R., M.C., C.G., C.A.S., I.S.N., A.M.F., D.Q., S. F., R.R., M.S. and E.M. acquired data. J.D.D.S. and A.P. analyzed and interpreted the data. J.D.D.S. and A.P. drafted the article. All authors revised the manuscript and provided final approval for publication.
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Patient consent was not required and waived by the host institution as all data were obtained by a retrospective analysis of non-identifiable clinical data from the hospital’s electronic records.
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Da Silva, J.D., Pereira, Â., Soares, A.R. et al. Diagnostic accuracy and the first genotype–phenotype correlation in glycogen storage disease type V. Pediatr Res (2023). https://doi.org/10.1038/s41390-023-02943-1
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DOI: https://doi.org/10.1038/s41390-023-02943-1
