Further Clinical and Biochemical Phenotype of GLA p.A143T: A Fabry Disease Newborn Screening Experience.

Background: In 2015, Illinois added Fabry disease to the newborn screening (NBS) panel, and numerous individuals who have the controversial p.A143T GLA variant were identified. Ann & Robert H. Lurie Children's Hospital of Chicago identified 80 individuals with this variant.

Summary: Of the 80 individuals, 34/80 were identified by NBS, 2/80 were identified by gene panel testing, and 44/80 were identified by cascade testing. These individuals were from 36 families and ranged in age from 7 months to 71 years. Most individuals identified by NBS were male (90.9%) and 35.96% had the p.A143T variant. All newborns with known pathogenic or likely pathogenic variants in GLA had enzyme leukocyte activities below 20% of the percentage of mean of normal. This threshold could serve as a guideline for determining risk of symptom development for p.A143T and other variants of unknown significance. No person with p.A143T had significant lyso-GL3 elevation in this cohort.

Key messages: These data suggest the variant impacts enzyme levels, but its effect on health outcomes remains unclear. We further characterize clinical and biochemical data on individuals with the p.A143T GLA variant to help provide guidance on its clinical significance.