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.

Keywords: CDSP; CTD; CUD; NBS; PCD; newborn screening; primary carnitine deficiency.

Figure 1

A world map of primary carnitine deficiency newborn screening programs, according to national NBS societies and the literature (created on mapchart.net, accessed on 27 October 2022).

Figure 2

The three-step screening algorithm for PCD as proposed by the CNCDN and G2M working group. Cut-offs are set for the method using underivatized-based sample preparation.