Gaps in Research

• Variable and possible late onset (>10 years) of the disease
• Unclear if those at highest risk of serious symptoms can be discerned in newborns
• Lack of published data of preventive treatment early in life
• Some risk of immunologic response to enzyme replacement therapy
• Need for a prospective study of screening and therapeutic intervention to demonstrate the benefit of newborn screening for Fabry Disease

• Pilot study in a US population
• Using a technology likely to be employed in the US (e.g. MS/MS)
• DACHDNC's recommendation has been referred to the Interagency Coordinating Center on Newborn and Child Screening (ICC) for additional review and imput \

• No population- based data is available, although some clinical studies derived from major referral centers are reported
• Discerning type A from B is not always possible to help predict the phenotypic range of those children who will be identified through population-based screening
• Characteristics of the screening test(s) are unknown since no population- based assessments have been performed
• No published studies are available to show the efficacy of treatment in humans especially for those most likely to benefit early in life, although clinical trials are underway
• No FDA approved treatment currently exists
• Need for pilot studies of the newborn screening test and treatment protocols

• Implementation of prospective pilot studies of the screening method by one or more traditional public health laboratories to test the reproducibility of the preliminary findings by Dr. Thomas Prior’s laboratory at the Ohio State University

• EIKD, The Condition: need consensus about the case definition of what constitutes Early Infantile Krabbe Disease (EIKD)
• Test for EIKD, Screening and Diagnosis: there is a need for additional information about the testing algorithm for EIKD. It is important to ascertain whether testing for Krabbe disease would be a stand alone test or done with multiplex testing, in part because of the cost implications
• Treatment for EIKD: More information is needed about the specific benefits of Hematopoietic Stem Cell Transplant (HSCT) to treat patients and what mutations would benefit most from HSCT

No issues identified

• What proportion of children would benefit from condition-specific treatment? There is a lack of follow-up data on screen positive children.
• What is the variation in prevalence across the United States?
• Does early identification improve the health of identified children?
• What is the threshold for moving a target from secondary status to one of the core targets?
• In terms of infrastructure, what are the expectations for newborn screening laboratories, public health clinicians, and families if there is a move from secondary to a primary target?

SACHDNC recommends the addition of screening for CCHD to the recommended uniform screening panel with the understanding that the following activities will also take place in a timely manner:

1. The National Institutes of Health shall fund research activities to determine the relationships among the screening technology, diagnostic processes, care provided, and the health outcomes of affected newborns with CCHD as a result of prospective newborn screening;
2. The Centers for Disease Control and Prevention shall fund surveillance activities to monitor disease link to infant mortality and other health outcomes;
3. The Health Resources and Services Administration shall guide the development of screening standards and infrastructure needed for the implementation of a public health approach to point of service screening for CCHD;
4. The Health Resources and Services Administration shall fund the development of, in collaboration with public health and health care professional organizations and families, appropriate education and training materials for families and public health and health care professionals relevant to the screening and treatment of CCHD.

No issues identified