Diagnostic accuracy and the first genotype–phenotype correlation in glycogen storage disease type V

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.