At-Risk Testing for Pompe Disease Using Dried Blood Spots: Lessons Learned for Newborn Screening
Open Access
- 21 December 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Neonatal Screening
- Vol. 6 (4), 96
- https://doi.org/10.3390/ijns6040096
Abstract
Pompe disease (GSD II) is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme acid-α-glucosidase (GAA, EC 3.2.1.20), leading to generalized accumulation of lysosomal glycogen especially in the heart, skeletal, and smooth muscle, and the nervous system. It is generally classified based on the age of onset as infantile (IOPD) presenting during the first year of life, and late onset (LOPD) when it presents afterwards. In our study, a cohort of 13,627 samples were tested between January 2017 and December 2018 for acid-α-glucosidase (GAA, EC 3.2.1.20) deficiency either by fluorometry or tandem mass spectrometry (MS). Testing was performed for patients who displayed conditions of unknown etiology, e.g., CK elevations or cardiomyopathy, in the case of infantile patients. On average 8% of samples showed activity below the reference range and were further assessed by another enzyme activity measurement or molecular genetic analysis. Pre-analytical conditions, like proper drying, greatly affect enzyme activity, and should be assessed with measurement of reference enzyme(s). In conclusion, at-risk testing can provide a good first step for the future introduction of newborn screening for Pompe disease. It yields immediate benefits for the patients regarding the availability and timeliness of the diagnosis. In addition, the laboratory can introduce the required methodology and gain insights in the evaluation of results in a lower throughput environment. Finally, awareness of such a rare condition is increased tremendously among local physicians which can aid in the introduction newborn screening.Keywords
This publication has 32 references indexed in Scilit:
- Multiplex newborn screening for Pompe, Fabry, Hunter, Gaucher, and Hurler diseases using a digital microfluidic platformClinica Chimica Acta; International Journal of Clinical Chemistry, 2013
- Oligosaccharide Analysis in Urine by MALDI-TOF Mass Spectrometry for the Diagnosis of Lysosomal Storage DiseasesClinical Chemistry, 2013
- Predicting cross‐reactive immunological material (CRIM) status in Pompe disease using GAA mutations: Lessons learned from 10 years of clinical laboratory testing experienceSeminars in Medical Genetics, Part C of the American Journal of Medical Genetics, 2012
- Consensus treatment recommendations for late‐onset Pompe diseaseMuscle & Nerve, 2011
- The effect of preparation, storage and shipping of dried blood spots on the activity of five lysosomal enzymesClinica Chimica Acta; International Journal of Clinical Chemistry, 2011
- Comparative Triplex Tandem Mass Spectrometry Assays of Lysosomal Enzyme Activities in Dried Blood Spots Using Fast Liquid Chromatography: Application to Newborn Screening of Pompe, Fabry, and Hurler DiseasesAnalytical Chemistry, 2011
- Diagnostic efficacy of the fluorometric determination of enzyme activity for Pompe disease from dried blood specimens compared with lymphocytes—possibility for newborn screeningJournal of Inherited Metabolic Disease, 2009
- Early Treatment With Alglucosidase Alfa Prolongs Long-Term Survival of Infants With Pompe DiseasePediatric Research, 2009
- Comparison of maltose and acarbose as inhibitors of maltase-glucoamylase activity in assaying acid α-glucosidase activity in dried blood spots for the diagnosis of infantile Pompe diseaseGenetics in Medicine, 2006
- The Natural Course of Infantile Pompe’s Disease: 20 Original Cases Compared With 133 Cases From the LiteraturePEDIATRICS, 2003