From the New York Times Sunday Magazine to GIM…

see page 51

The National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) has garnered considerable attention in the medical and lay communities, having been featured, for example, on the cover of the New York Times Sunday Magazine in 2009. GIM is delighted to publish the first systematic analysis of that program’s experience over its first two years. Study participants were selected in a rigorous process to characterize and assess the possibility of determining the etiology of their enigmatic disorder. Each accepted participant was extensively phenotyped, and a subset of participants and selected family members were subjected to an integrated set of genomic analyses, including high-density single-nucleotide-polymorphism arrays and whole-exome and whole-genome analysis. From 1,191 medical records reviewed, 326 patients were accepted for the program, of whom 160 were admitted directly to the NIH clinical care center. Of this group, 53% had neurological disorders and 47% were children. Diagnoses were reached in 24% of patients on clinical, biochemical, pathological, or molecular grounds. Twenty-one diagnoses involved rare or ultra-rare diseases, and two new disorders were discovered. The UDP addresses an important need, and its substantial reliance on emerging genomic technologies highlights the importance of our field as genomics increasingly informs medical practice.

Newborn screening: making hard calls

see page 129

Decisions regarding which disease entities should be included in newborn screening (NBS) are difficult. The task is further complicated by advances in technology that have enabled NBS for a multitude of inborn errors. In this issue, Petros proposes a framework for use by public health practitioners as they struggle with these decisions. This framework expands on the now classic Wilson-Jungner criteria with the addition of 11 criteria specific to NBS. A calculation that the author refers to as the pNBS (proposed (or prototype) newborn screening) decision score is used to quantify results and rank candidate disorders. The scoring system designates phenylketonuria, cystic fibrosis, and Pompe disease for inclusion but suggests that Krabbe disease not be screened for at this time. This proposed framework should assist policy makers in making difficult NBS decisions and can be seen as a valuable first step toward revisiting the Wilson-Jungner criteria in a new era of medicine.