Neurológia pre prax 4/2021

Diaphragm respiration disorder as first clinical manifestation in adult form of Pompe disease

Adult form of Pompe disease is a rare inherited autosomal recessive metabolic disorder caused by deficiency of lysosomal acid α -glucosidase activity. It is characterised by the accumulation of glycogen in muscle tissue that leads to progressive muscle weakness – myopathy. The clinical hallmark of adult-onset Pompe disease is slowly progressive myopathy. However, adult forms present themselves with certain phenotypic diversity which causes difficulties in diagnosing and diagnostic pitfalls. The course of adult Pompe form disease was usually progressive, disabling and often fatal. There was no treatment for Pompe disease until the end of 20th century. The recent development in enzymatic replacement therapy with recombinant α-glucosidase has dramatically improved the life expectancy and quality of life with improvements of muscle motor and muscle respiratory functions. EMA and FDA confirmed in 2006 indication for enzymatic replacement therapy in all 3 Pompe disease forms – infantile, juvenile and adult. The best results are achieved in patients with Pompe disease diagnosed in early stages. Late diagnosis in advanced stages deprives the benefits of enzymatic replacement therapy with significant impact on patients´ prognosis. Therefore, early diagnosis of adult Pomce disease is of crucial importance. Several studies in 21st century confirmed that the sooner you begin with enzymatic replacement therapy, the bigger is the probability of improving the clinical symptoms of the disease. Dried blood spot test provides a rapid and reliable screening method for determination of α-glucosidase deficiency. Slovak Republic joined this screening programme in 2009. Before 2009 there was no patient with adult Pompe disease form diagnosed in SR. After 2009 we diagnosed with dried spot test adult Pompe disease in 10 patients. The diagnosis was definitively confirmed by measurement of decreased enzyme activity in leukocytes, and by DNA testing with verification of pathogenic mutations in gene for α-glucosidase. For its rare occurrence adult Pompe disease form is an underdiagnosed disease. Adult form is also characterised by heterogeneity of muscle symptoms causing diagnostic pitfalls. All 10 patients with adult form were initially diagnosed with false diagnoses. The average time between initial disease symptoms and correct diagnosis statement of Pompe diseases was 7.1 years (2–14years). We report in our paper several essential errors which delayed the determination of correct diagnosis and early prescription of enzymatic replacement therapy. We also present a rare case-report of 63-year-old female with diaphragm respiration disorder as first clinical manifestation of adult form of Pompe disease.

Keywords: adult Pompe disease form, α-glucosidase deficiency, myopathy, false diagnosis, diaphragm respiration disorder, enzyme investigation, DNA diagnosis, enzymatic replacement therapy