Related Experiment Video
Updated: Jul 9, 2025
Biochemical Titration of Glycogen In vitro
Published on: November 24, 2013
Diagnostic accuracy and the first genotype-phenotype correlation in glycogen storage disease type V
Jorge Diogo Da Silva1,2,3,4, Ângela Pereira5,6, Ana Rita Soares7,8
1Centro de Genética Médica Doutor Jacinto Magalhães (CGM), Centro Hospitalar Universitário de Santo António, Porto, Portugal. jorge.dcr.silva@gmail.com.
Insights
Glycogen storage disease type V (GSDV) is often diagnosed late, even in adulthood, despite early symptoms. This study identifies clinical and genetic factors that can aid in earlier diagnosis of this underdiagnosed metabolic disorder.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Glycogen storage disease type V (GSDV) is an underdiagnosed autosomal recessive metabolic disorder.
- It is caused by pathogenic PYGM variants and often presents with exercise intolerance in children.
Purpose of the Study:
- To assess diagnostic timing and accuracy of GSDV.
- To identify potential clinical and analytical predictors for earlier diagnosis.
Main Methods:
- Retrospective review of 28 GSDV cases from a tertiary hospital.
- Assessment of clinical information from pediatric and adult metabolic disease consultations.
Main Results:
- Over 90% of cases were diagnosed late, with over 50% diagnosed in adulthood despite preschool symptom onset.
- Myoglobinuria was associated with an earlier diagnostic age.
- The R50* variant showed a dosage-dependent association with increased myoglobinuria and CK elevation.
Conclusions:
- GSDV is severely underdiagnosed and frequently misdiagnosed.
- Clinical and analytical factors can indicate GSDV diagnosis.
- The first genotype-phenotype correlation for GSDV, specifically the R50* variant, was established.
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:
GSDV is a pediatric-onset metabolic disorder that is mostly diagnosed late in the adult age and commonly misdiagnosed. We observed the first genotype-phenotype correlation in GSDV, regarding the common R50* variant. Awareness of GSDV for pediatricians and the overall medical community is vital.
More Related Videos
Related Concept Videos
01:22Lysosomal Hydrolases
01:20Inborn Errors of Metabolism
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...