Abstract 8: Facilitating Hematopoietic Cell Transplant for Patients with Infantile Krabbe Disease Identified by Newborn Screening

Abstract Introduction Krabbe disease is a rare lysosomal storage disease characterize by the deficiency of galactocerebrosidase (GALC), essential for the turnover of myelin in the nervous system. In its most severe form, infantile Krabbe disease (IKD), symptoms appear before 12 months of age and patients die before 2 years of age. Hematopoietic cell transplant (HCT) using cord blood performed <30 days of age has been shown to improve survival and neurological function of affected babies. The timeline for diagnosis to transplant creates unique challenges to be addressed. Objectives Describe steps from a positive newborn screen (NBS) to timely transplantation for IKD. Methods Data review and discussion with experts treating IKD Results Currently 12 US states perform NBS for IKD. Enzymatic activity of GALC is measured using dried blood samples. Samples with low GALC activity undergo second tier testing of Psychosine (PSY). A PSY >10 confirms the diagnosis of IKD. Over the past 17 years, >6M babies have been screened and ~25 newborns diagnosed with IKD Discussion In 2024, IKD was added to the Recommended Uniform Screening Panel (RUSP) which means that additional states will be adding IKD to their NBS panels in the next few years. Given the short timeline from diagnosis to transplant, each state should develop a KD NBS Preparedness algorithm to ensure affected babies have access to treatment. The roadmap for preparedness includes (1) rapid PSY testing, (2) Communication of results to a physician familiar with IKD who can talk with the parents, (3) An established partnership with a pediatric transplant center willing to take urgent referrals, (4) Repeat disease testing, mutational analysis, and HLA typing (*do not wait for mutation results to proceed to transplant), (5) transfer of baby from Mom’s to their own insurance; (6) Counselling of parents and referral to TC, (7) inpatient workup, (8) placement of CVL and G-Tube prior to chemo, (9) testing of candidate cord blood units for CT and GALC level, (10) initiation of chemotherapy regardless of bilirubin and also before final cord blood unit is identified. Additional details about the roadmap to transplant and transplant preparedness will be discussed.