Joseph Orsini, PhD

The primary research aim of the newborn screening lysosomal storage disease (LSD) and X-linked adrenoleukodystrophy (X-ALD) screening laboratory is to simplify and automate published low capacity newborn screening assays in order to transform them into high capacity assays.  The lab was the first in the world to implement newborn screening for Krabbe disease and we have supported others who have an interest in implementing this testing.  We have screened over two million infants to date.  Infants with low activity by the screen test are subjected to DNA sequencing of the GALC gene, which has helped us to gain a better understanding of the mutations and effect on Krabbe disease symptoms. In collaboration with Dr. Zhang and Dr. Chuang, from Genzyme, we developed an assay that could detect psychosine in dried blood spots.  Psychosine is a co-substrate of galactocerebrosidase and it is thought to play a role in the development of Krabbe disease. Psychosine testing of dried blood spots from infants with infantile Krabbe disease showed these patients had elevated psychosine concentrations, whereas infants with low GALC activity and two mutations in the GALC gene did not have elevated psychosine. This work was very important as it suggested that individuals with the infantile form of Krabbe disease, which requires immediate treatment, could be identified by the elevated concentrations.  Further work is needed to determine if psychosine concentrations in blood can be used to monitor asymptomatic infants with low GALC enzyme activity to determine if the psychosine levels can be used as an early predictor of later onset Krabbe disease. 

In addition, the laboratory was the first to implement a high volume test for X-ALD and we were the second laboratory in the US to implement screening for Pompe disease.  Gene sequencing is done on all screen positives for both of these disorders, which helps the medical community in the associated follow-up work that is performed on these infants that is required to achieve a diagnosis.

The LSD/ALD screening laboratory is currently performing grant-funded pilot screening for four other lysosomal storage disorders: Gaucher disease, Hurler’s disease, Niemann Pick A/B disease, and Fabry disease. This work is sponsored by the Mt. Sinai School of Medicine.  This study is designed to evaluate the ethical, legal, and social issues associated with screening for late onset disorders via newborn screening.