Newborn screening for Krabbe disease in New York State: the first eight years’ experience

Precision newborn screening for lysosomal disorders

“…10 Other lysosomal disorders, particularly galactocerebrosidase (GALC) deficiency (Krabbe disease), 11 have been turned down by the committee because they lacked evidence of net benefits. However, advocacy efforts and legislative mandates have propelled six states to begin screening for Krabbe disease and other lysosomal disorders, [12][13][14] but reports of outcomes and performance have not been encouraging. [15][16][17] In 2015, the legislature of the Commonwealth of Kentucky passed bill KRS 214.155, mandating screening for Krabbe disease.…”

“…18 This request was not fulfilled because conventional interpretation methods of a single marker (cutoff, percent of daily mean) are not suited to differentiation of affected patients from individuals who are either heterozygous or carry pseudo-deficiency alleles. [12][13][14][15] The laboratory made a counter-proposal to perform a profile of six lysosomal enzyme activities using commercially available substrates, inclusive of the primary markers of Pompe disease and MPS I, integrated with additional analytes and second-tier tests as needed. This new plan, characterized by the expanded scope of testing and reporting of three conditions, was agreeable to both Kentucky and Mayo Clinic.…”

Moonlighting newborn screening markers: the incidental discovery of a second-tier test for Pompe disease

“…16 To minimize the number of false-positive results requiring unnecessary patient contact, genotyping of borderline cases has been adopted as for other lysosomal disorders. 17 At the biochemical level, the Taiwan newborn screening program proposed to calculate the neutral α-glucosidase to GAA ratio. 18 Second-tier tests have shown clinical utility for other lysosomal disorders, 19,20 but no other known marker of Pompe disease measurable in blood spots has been described yet.…”

Should states adopt newborn screening for early infantile Krabbe disease?

“…1 The article in this issue of Genetics in Medicine provides an important update on the technical success of the largest cohort of individuals undergoing such mandated screening. 2 As such, it is a valuable source of information on the real-world effects of such deployment and contributes significant new data compared with that reviewed just over 6 years ago by what is now known as the US Department of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children. 3 In Wisconsin, a framework for evaluating the addition or deletion of testing was proposed to the Wisconsin Secretary of Health in June 2013 (Report to the Secretary of the Wisconsin Department of Health Services: Newborn Screening Task Force, June 2013).…”

“…As part of this consideration, I reviewed the previous work of the federal advisory committee and more than 1,000 new abstracts. In preparing this Commentary, I also reviewed the article by Orsini et al 2 in this issue. A summary of these findings is compared with the "Wisconsin addition criteria" to evaluate the implications these new data have for the decision as to whether to adopt or remove NBS for EIKD.…”