Alpha Glucosidase Assay on Dried Blood Spot in the Early Diagnosis of Infantile Pompe Disease

Abstract

Infantile-onset Pompe disease (IOPD) presents with hypotonia, muscle weakness, motor delay, cardiomyopathy, feeding problems, and respiratory insuffi ciency. An early diagnosis is important to start enzyme replacement therapy (ERT) early. 1 Alpha-glucosidase (GAA) enzyme assay on dried blood spots (DBS) allows a diagnosis of Pompe disease (PD) more simple and fast. GAA assay on DBS is reliable, non-invasive, sensitive, and specifi c. It is a quick and cheap test, and requires only a very small quantity of blood to be collected, which allows for a non-invasive test in a newborn who presents a clinical suspect of PD. In the last 6 years, we identifi ed 9 children affected by IOPD by GAA assay on DBS in tandem-mass spectrometry (MS/MS): 8 of them presented classic IOPD and 1 presented non-classic IOPD. At diagnosis, all patients showed cardiomyopathy. Five patients diagnosed in the fi rst month of life (range 2-20 days; mean 10.2 days; median 9 days) showed cardiomyopathy: two of them presented respiratory distress. Four patients diagnoses in the infantile age (range 2-15 months; mean 8 months; median 6.5 months) presented hypertrophic cardiomyopathy and hypotonia. The GAA activity on DBS was near absent in all the patients, ranging from 0 to 0.2 μmol/L/h (n.v. 2.31-27.4). The GAA activity in lymphocytes was confi rmed to be low in all the patients (range 0-0.8 nmol/mg/h, n.v. 11-32). Molecular analysis of the GAA gene confi rmed the diagnosis of