Diagnostic delays are common in Pompe disease, hampered by its rarity, variable clinical presentation and signs and symptoms that overlap with other neuromuscular disorders.1
Analysis of data from 647 evaluable patients enrolled in the Pompe Disease Registry has found that a diagnostic gap between age at symptom onset and age at diagnosis exists across the spectrum of Pompe disease.1 The diagnostic gap was shortest (1.4 months; minimum 0.0 months; maximum 13.9 months) in patients with classic infantile-onset Pompe disease (Group A), who have the most severe and rapidly progressing phenotype. It was longest in those patients with either non-classic infantile-onset disease or with symptom onset between 13 months and 12 years of age (Group B; 12.6 years, minimum 0.0 years; maximum 60.0 years). Amongst those patients with symptom onset after 12 years of age (Group C), the diagnostic gap was 6.0 years (minimum 0.0 years; maximum 49.8 years).
Diagnostic gap in patients with Pompe disease.
Adapted from Kishnani et al. Am J Med Genet Part A 161A:2431–2443.1
Group A = patients with onset of signs or symptoms ≤12 months of age with evidence of cardiomyopathy.
Group B = patients with onset of signs or symptoms ≤12 months of age without evidence of cardiomyopathy and onset of signs or symptoms >12 months to ≤12 years of age.
Group C = patients with onset of signs or symptoms >12 years of age.
Diagnosis of Pompe disease occurred earlier in patients with concurrent musculoskeletal and respiratory symptoms as the presenting symptoms. The presenting sign or symptom class was found to be a significant independent predictor of a long diagnostic gap in all three groups, whereas age at symptom onset and year of diagnosis were significant predictors only in groups B and C. Body mass index and gender were not significant independent predictors of diagnostic delay.
Diagnostic tools (dried blood spot [DBS] testing) and a disease-specific treatment is available for Pompe disease. Newborn screening programs can measure acid α-glucosidase (GAA) enzyme activity in DBSs providing an opportunity for early diagnosis and treatment.2 Potential diagnostic delays in late-onset could be avoided by testing GAA enzyme activity in patients who present with signs or symptoms suggestive of Pompe disease rather than waiting for the onset of additional signs or symptoms.1, 3