Newborn bloodspot screening for Pompe disease

Background

This work is part of the activity "Improving and developing methods for early diagnosis of several lysosomal storage disorders" within the project "Sustainable Orphan Drug Development through Registries and Monitoring" at the Top Institute Pharma (www.tipharma.com, project no. T6-208 ), funded by the Health Insurance Board (College voor Zorgverzekeringen), Steering Committee on Orphan Drugs (Stuurgroep Weesgeneesmiddelen), Genzyme Corp., Shire, Academic Medical Center (Amsterdam), Erasmus Medical Center (Rotterdam), and Utrecht Medical Center .

Treatment has become available for several of the lysosomal storage disorders including Pompe -, Hurler-, Hunter- and Fabry disease. Early diagnosis and early intervention is to the benefit of patients and their families and increases the chance to achieve an optimal therapeutic effect.

The ultimate way to speed up diagnosis is universal newborn screening. Two promising techniques have emerged that can in principle be used: one is measuring the activity of lysosomal enzymes in blood spots with artificial substrates that are converted to a fluorescent product, the other is using artificial substrates that are converted to products with specific mass that are detected by Tandem Mass spectrometry.

Thanks to these developments in both therapy as well as screening methodologies, some of the lysosomal storage disorders may soon meet the criteria set by the Health Council of the Netherlands in 2005 for the national blood-spot screening program for newborns. Most lysosomal diseases have a broad clinical spectrum and newborn screening will probably not just identify patients who will develop symptoms within a few months after birth, but also persons who will develop symptoms at later age.

The disease(s) addressed in this project can be taken as prototype for other very rare but treatable lysosomal storage disorders with broad clinical spectrum. At present there are insufficient data for evaluating the advantages and disadvantages of newborn screening for these diseases. While there is no gold standard for the evaluation of new screening tests, several frameworks have been developed.