Targeted population screening of late onset Pompe disease in unspecified myopathy patients for Korean population

Neuromuscul Disord. 2017 Jun;27(6):550-556. doi: 10.1016/j.nmd.2017.03.005. Epub 2017 Mar 10.

Abstract

We performed targeted population screening of late onset Pompe disease (LOPD) in unspecified myopathy patients, because early diagnosis is difficult due to its heterogeneous clinical features. We prospectively enrolled 90 unrelated myopathic patients who had one or more signs out of five LOPD-like clinical findings (proximal weakness, axial weakness, lingual weakness, respiratory difficulty, idiopathic hyperCKemia). Acid alpha glucosidase activity was evaluated with dried blood spot and mixed leukocyte simultaneously. For a final diagnosis of LOPD, 16 patients with decreased enzyme activity were genotyped by GAA molecular analysis. We found two patients with LOPD (2.2%), and the remaining 14 patients had at least one G576S or E689K mutation, known as the pseudodeficiency allele. Acid alpha glucosidase activity of LOPD patients was significantly lower than that of patients with at least one pseudodeficiency allele (p = 0.017). This study is the first LOPD screening study for targeted Korean population, and more generally, an Asian population. Our findings suggest that for diagnosis of LOPD in Asian population, modified cutoff value of acid alpha glucosidase activity with dry blood spot considering that of patients having heterozygote pathogenic variants or pseudodeficiency alleles may reduce time and cost requirements and increase the comfort of patients.

Keywords: Late onset Pompe disease; Pseudodeficiency; Screening study; Unspecified myopathies.

MeSH terms

  • Adult
  • Female
  • 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
  • Muscular Diseases / blood
  • Muscular Diseases / complications
  • Muscular Diseases / diagnosis*
  • Muscular Diseases / enzymology
  • Prospective Studies
  • Republic of Korea / epidemiology
  • alpha-Glucosidases / blood

Substances

  • GAA protein, human
  • alpha-Glucosidases