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 PD in all the patients. Five patients are being followed up at our department, and ERT was started at diagnosis at a standard dose of 20 mg/kg every 2 week. All these patients demonstrated a progressive improvement of cardiomyopathy. The individual response to ERT was different in the group of patients due to CRIM-status, development of rhGAA specifi c antibodies, age of presentation, and rate of disease progression, in accordance with literature data.2 In IOPD, an early diagnosis is important to start early ERT, which has been shown to be effective in treating patients with IOPD and late-onset PD. GAA assay on DBS is a reliable, non-invasive, sensitive, and specifi c test for newborns and infants in the fi rsts months of life with signs or symptoms of PD. There is a PD newborn screening pilot program in the Tuscany and Umbria regions.