Identification of patients with Pompé disease using routine pathology results: PATHFINDER (creatine kinase) study

Adult-onset inherited errors of metabolism can be difficult to diagnose. Some cases of potentially treatable myopathy are caused by autosomal recessive acid α-1,4 glucosidase (acid maltase) deficiency (Pompé disease). This study investigated whether screening of asymptomatic patients with elevated creatine kinase (CK) could improve detection of Pompé disease.

Pathology databases in six hospitals were used to identify patients with elevated CK results (>2× upper limit of normal). Patients were recalled for measurement of acid α-1,4 glucosidase activity in dried blood spot samples.

Samples were obtained from 812 patients with elevated CK. Low α-glucosidase activity was found in 13 patients (1.6%). Patients with neutropaenia (n=4) or who declined further testing (n=1) were excluded. Confirmation plasma specimens were obtained from eight individuals (1%) for a white cell lysosomal enzyme panel, and three (0.4%) were confirmed to have low α-1,4-glucosidase activity. One patient was identified as a heterozygous carrier of an acid α-1,4 glucosidase c.-32-13 G>T mutation. Screening also identified one patient who was found to have undiagnosed Fabry disease and one patient with McArdle's disease. One patient later presented with Pompé's after an acute illness. Including the latent case, the frequency of cases at 0.12% was lower than the 2.5% found in studies of patients with raised CK from neurology clinics (p<0.001).

Screening pathology databases for elevated CK may identify patients with inherited metabolic errors affecting muscle metabolism. However, the frequency of Pompé's disease identified from laboratory populations was less than that in patients referred for neurological investigation.