Newborn Screening for Mucopolysaccharidosis Type I: Past, Present and Future

Abstract

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by a deficiency of the lysosomal hydrolase α-L-iduronidase. MPS I is characterized by a broad range of disease manifestations. This includes devastating neurocognitive and bone manifestations and a short life expectancy in severely affected MPS I patients. Neurocognitive manifestations are typically limited in more attenuated MPS I, but patients may still suffer from severe somatic and bone manifestations. Severe MPS I patients are primarily treated with hematopoietic stem cell transplantation (HSCT) and more attenuated patients with enzyme replacement therapy. HSCT should be initiated before irreversible disease manifestations, preferably before 9 months, but may be initiated in patients up to 2 years. Early diagnosis of MPS I is challenging at best, and newborn screening (NBS) has already been initiated in several countries to diagnose and treat patients early. This article summarizes the history, benefits, methods and challenges that have to be addressed before NBS can be used most effectively.