Screening for Pompe disease in Serbian patients with limb-girdle muscle weakness

Abstract

Introduction/aims: Patients with late-onset Pompe disease (LOPD) can be found among individuals with limb-girdle muscle weakness, as well as among individuals with isolated weakness of trunk and respiratory muscles. Some patients with asymptomatic hyperCKemia may have Pompe disease. Aim of this research was analysis of the frequency of LOPD among Serbian patients with unexplained limb-girdle muscle weakness, and/or respiratory muscle weakness, and/or hyperCKemia.

Methods: Analysis of acid alpha-glucosidase (GAA) activity was performed using tandem mass spectrometry in a sample of a dry blood spot. In patients who were found to have decreased enzyme activity, DNA was isolated from a dry blood spot and sequencing of the GAA gene was performed.

Results: During a 4.5-year period, 138 patients suspected of having LOPD were sent for the analysis. The average age at the time of testing was 44.3 ± 15.7 years, and symptoms duration was 7.3 ± 7.6 years. Mean GAA activity was 4.6 ± 1.9 umol/L/h. Decreased enzyme activity was observed in 10 (7 %) patients. Genetic analysis of the GAA gene was performed in these ten, and four (3 %) were diagnosed with LOPD.

Conclusion: In the Serbian cohort of 138 patients with limb-girdle muscle weakness and/or respiratory muscle weakness and/or hyperCKemia, 3 % had genetically confirmed LOPD. All diagnosed patients received enzyme replacement therapy which alters the course of the disease.

Keywords: Acid alpha-glucosidase; Dry blood spot; GAA gene; Late-onset Pompe disease; Limb-girdle muscle weakness.