Newborn Screening of Primary Carnitine Deficiency: An Overview of Worldwide Practices and Pitfalls to Define an Algorithm before Expansion of Newborn Screening in France

Abstract

Primary Carnitine Deficiency (PCD) is a fatty acid oxidation disorder that will be included in the expansion of the French newborn screening (NBS) program at the beginning of 2023. This disease is of high complexity to screen, due to its pathophysiology and wide clinical spectrum. To date, few countries screen newborns for PCD and struggle with high false positive rates. Some have even removed PCD from their screening programs. To understand the risks and pitfalls of implementing PCD to the newborn screening program, we reviewed and analyzed the literature to identify hurdles and benefits from the experiences of countries already screening this inborn error of metabolism. In this study, we therefore, present the main pitfalls encountered and a worldwide overview of current practices in PCD newborn screening. In addition, we address the optimized screening algorithm that has been determined in France for the implementation of this new condition.

Collaborative evaluation study on 18 candidate diseases for newborn screening in 1.77 million samples

“…Thus, in addition to the low PPV, individuals with a possibly benign phenotype were identified in a significant proportion of cases. To increase specificity and PPV, it has been proposed using supplemental biomarkers in addition to C0, coupling SLC22A5 sequencing or second blood sampling at a later age 35 . In the absence of a suitable screening strategy for the reliable detection of clinically relevant CTD within the first days of life, CTD does not seem to be suitable to be included in NBS panels.…”

A qualitative study on the perspectives of mothers who had been diagnosed with primary carnitine deficiency through newborn screening of their child

“…Primary carnitine deficiency (OCTN2 deficiency, OMIM #212,140) is an inborn error of metabolism, in which low carnitine levels result in impairment of oxidation of long chain fatty acids. Birth prevalence has been reported to be 1 in 30,000-142,000 [ 1 ]. It is caused by bi-allelic pathogenic variants in the SLC22A5 gene [ 2 ].…”

“…With the use of tandem mass spectrometry (MS/MS) technology, it is possible to detect low free carnitine levels in neonatal bloodspot screening (NBS), and hence identify primary carnitine deficiency in newborns [ 1 , 4 ], enabling early treatment. In many instances, however, the reduced carnitine level is not caused by primary carnitine deficiency in the child, but in the mother [ 5 ].…”