dépistage néonatal

Newborn screening (NBS) programmes are considered to be one of the most successful secondary prevention measures in childhood to prevent or reduce morbidity and/or mortality via early disease identification and subsequent initiation of therapy. However, while many rare diseases can now be detected at an early stage using appropriate diagnostics, the introduction of a new target disease requires a detailed analysis of the entire screening process, including a robust scientific background, analytics, information technology, and logistics. In addition, ethics, financing, and the required medical measures need to be considered to allow the benefits of screening to be evaluated at a higher level than its potential harm. Infantile nephropathic cystinosis (INC) is a very rare lysosomal metabolic disorder. With the introduction of cysteamine therapy in the early 1980s and the possibility of renal replacement therapy in infancy, patients with cystinosis can now reach adulthood. Early diagnosis of cystinosis remains important as this enables initiation of cysteamine at the earliest opportunity to support renal and patient survival. Using molecular technologies, the feasibility of screening for cystinosis has been demonstrated in a pilot project. This review aims to provide insight into NBS and discuss its importance for nephropathic cystinosis using molecular technologies.

Newborn screening (NBS) programmes are essential in the diagnosis of inherited metabolic diseases (IMDs) and for access to disease modifying treatment. Most European countries follow the World Health Organisation (WHO) criteria to determine which disorders are appropriate for screening at birth; however, these criteria are interpreted and implemented by individual countries differently, creating disparities. Advances in research and diagnostics, together with the promise of new treatments, offer new possibilities to accelerate the expansion of evidence-based screening programmes. A novel and robust algorithm was built to objectively assess and prioritise IMDs for inclusion in NBS programmes. The Wilson and Jungner classic screening principles were used as a foundation to develop individual and measurable criteria. The proposed algorithm is a point-based system structured upon three pillars: condition, screening, and treatment. The algorithm was tested by applying the six IMDs currently approved in the United Kingdom NBS programme. The algorithm generates a weight-based score that could be used as the first step in the complex process of evaluating disorders for inclusion on NBS programmes. By prioritising disorders to be further evaluated, individual countries are able to assess the economic, societal and political aspects of a potential screening programme.

This study assesses the benefits and challenges of using genomics in Newborn Screening Programs (NBS) from the perspectives of State program officials. This project aims to help programs develop policies that will aid in the integration of genomic technology. Discussion groups were conducted with the NBS Program and Laboratory Directors in the seven HRSA Regional Genomics Collaboratives (August 2014–March 2016). The discussion groups addressed expected uses of genomics, potential benefits, and challenges of integrating genomic technology, and educational needs for parents and other NBS stakeholders: Twelve focus groups were conducted, which included participants from over 40 state programs. Benefits of incorporating genomics included improving screening modalities, supporting diagnostic procedures, and screening for a wider spectrum of disorders. Challenges included the costs of genomics, the ability to educate parents and health care providers about results, and the potential negative psychosocial impact of genomic information. Attempts to address the challenges of integrating genomics must focus on preserving the child welfare goals of NBS programs. Health departments will need to explore how genomics could be used to enhance programs while maintaining universal access to screening.

X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder caused by pathogenic variants in the ATP-binding cassette subfamily D member 1 gene (ABCD1) that encodes the adrenoleukodystrophy protein (ALDP). Defects in ALDP result in elevated cerotic acid, and lead to C26:0-lysophosphatidylcholine (C26:0-LPC) accumulation, which is the primary biomarker used in newborn screening (NBS) for X-ALD. C26:0-LPC levels were measured in dried blood spot (DBS) NBS specimens using a flow injection analysis (FIA) coupled with electrospray ionization (ESI) tandem mass spectrometry (MS/MS) performed in negative ion mode. The method was validated by assessing and confirming linearity, accuracy, and precision. We have also established C26:0-LPC cutoff values that identify newborns at risk for X-ALD. The mean concentration of C26:0-LPC in 5881 de-identified residual routine NBS specimens was 0.07 ± 0.02 µM (mean + 1 standard deviation (SD)). All tested true X-ALD positive and negative samples were correctly identified based on C26:0-LPC cutoff concentrations for borderline between 0.15 µM and 0.22 µM (mean + 4 SD) and presumptive screening positive at ≥0.23 µM (mean + 8 SD). The presented FIA method shortens analysis run-time to 1.7 min, while maintaining the previously established advantage of utilizing negative mode MS to eliminate isobaric interferences that could lead to screening false positives.

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in ABCD1, which encodes the peroxisomal very-long-chain fatty acid transporter, causing a spectrum of neurodegenerative phenotypes. The childhood cerebral form of the disease is particularly devastating. Early diagnosis and intervention improve outcomes. Because newborn screening facilitates identification of at-risk individuals during their asymptomatic period, X-ALD was added to the Pennsylvania newborn screening program in 2017. We analyzed outcomes from the first four years of X-ALD newborn screening, which employed a two-tier approach and reflexive ABCD1 sequencing. There were 51 positive screens with elevated C26:0-lysophosphatidylcholine on second-tier screening. ABCD1 sequencing identified 21 hemizygous males and 24 heterozygous females, and clinical follow up identified four patients with peroxisomal biogenesis disorders. There were two false-positive cases and one false-negative case. Three unscreened individuals, two of whom were symptomatic, were diagnosed following their young siblings’ newborn screening results. Combined with experiences from six other states, this suggests a U.S. incidence of roughly 1 in 10,500, higher than had been previously reported. Many of these infants lack a known family history of X-ALD. Together, these data highlight both the achievements and challenges of newborn screening for X-ALD.