P003: Glucosylsphingosine and its utility for newborn screening for Gaucher disease*

Gaucher disease (GD) presents on a continuum of severity ranging from non-neuronopathic (GDI) to severe neuronopathic disease (GDII, GDIII) with approved treatments existing for GDI and GDIII but not yet for GDII. Several newborn screening (NBS) programs in the US and elsewhere have begun screening for GD by enzyme analysis. While this approach is highly sensitive, it is not definitive in determining disease or severity. Moreover, GBA genotype/phenotype correlations are limited. While the N409S variant either in homozygous state or compound heterozygous with another pathogenic allele predicts GDI, and the L483P variant either in homozygous state or in combination with a null allele is typically associated with neuronopathic disease (GDII or GDIII), only 29% of variants listed currently by ClinVar are of known significance.