Targeted screening for the detection of Pompe disease in patients with unclassified limb-girdle muscular dystrophy or asymptomatic hyperCKemia using dried blood: A Spanish cohort

Neuromuscul Disord. 2015 Jul;25(7):548-53. doi: 10.1016/j.nmd.2015.04.008. Epub 2015 Apr 23.

Abstract

We aimed to screen for Pompe disease in patients with unclassified limb-girdle muscular dystrophy (LGMD) or asymptomatic hyperCKemia using dried blood spot (DBS) assays. Subsequently, we aimed to calculate the diagnostic delay between initial symptom presentation and the diagnosis. A prospective, multicenter, observational study was conducted in 348 patients: 146 with unclassified LGMD and 202 with asymptomatic or paucisymptomatic hyperCKemia. We quantified levels of acid alpha-glucosidase (GAA) from dried blood spots analyzed fluorometrically. The test was positive in 20 patients, and Pompe disease was confirmed by genetic testing in 16. Undiagnosed Pompe disease was detected in 7.5% of patients with LGMD and in 2.5% of patients with persistent, idiopathic elevation of serum creatine kinase. The c.-32-13 T > G mutation was found most commonly. The diagnostic delay was 15 years on average. In conclusion, DBS tests are useful and reliable screening tools for Pompe disease. We recommend the dried blood spot test to be included in the diagnostic work-up of patients with unclassified myopathies with proximal weakness and/or hyperCKemia of unknown cause and, when positive, to define the diagnosis, it will have to be confirmed by biochemical and/or molecular genetic analysis.

Keywords: Creatine kinase; Dried blood spots; Enzyme replacement therapy; GAA deficiency; Glycogen storage disease; Myopathy.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Creatine Kinase / blood*
  • Delayed Diagnosis
  • Dried Blood Spot Testing*
  • Female
  • Genetic Testing
  • Glycogen Storage Disease Type II / blood*
  • Glycogen Storage Disease Type II / complications
  • Glycogen Storage Disease Type II / diagnosis*
  • Glycogen Storage Disease Type II / enzymology
  • Humans
  • Male
  • Metabolic Diseases / blood*
  • Metabolic Diseases / complications
  • Metabolic Diseases / genetics
  • Middle Aged
  • Muscular Dystrophies, Limb-Girdle / blood*
  • Muscular Dystrophies, Limb-Girdle / complications
  • Muscular Dystrophies, Limb-Girdle / enzymology
  • Mutation
  • Prospective Studies
  • Young Adult
  • alpha-Glucosidases / blood

Substances

  • Creatine Kinase
  • alpha-Glucosidases