27
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Adrenoleukodystrophy Newborn Screening in the Netherlands (SCAN Study): The X-Factor

      research-article
      1 , 2 , 1 , 3 , 4 , 4 , 5 , 6 , 4 , 7 , 7 , 5 , 8 , 9 , 1 , 1 , 5 , 8 , 10 , 1 , 10 , 9 , 1 , 1 , 2 , 11 , 7 , 1 , 11 , *
      Frontiers in Cell and Developmental Biology
      Frontiers Media S.A.
      adrenoleukodystrophy, peroxisomes, newborn screening, neonatal, gender, heel prick, dried bloodspots, X chromosome

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          X-linked adrenoleukodystrophy (ALD) is a devastating metabolic disorder affecting the adrenal glands, brain and spinal cord. Males with ALD are at high risk for developing adrenal insufficiency or progressive cerebral white matter lesions (cerebral ALD) at an early age. If untreated, cerebral ALD is often fatal. Women with ALD are not at risk for adrenal insufficiency or cerebral ALD. Newborn screening for ALD in males enables prospective monitoring and timely therapeutic intervention, thereby preventing irreparable damage and saving lives. The Dutch Ministry of Health adopted the advice of the Dutch Health Council to add a boys-only screen for ALD to the newborn screening panel. The recommendation made by the Dutch Health Council to only screen boys, without gathering any unsolicited findings, posed a challenge. We were invited to set up a prospective pilot study that became known as the SCAN study (SCreening for ALD in the Netherlands). The objectives of the SCAN study are: (1) designing a boys-only screening algorithm that identifies males with ALD and without unsolicited findings; (2) integrating this algorithm into the structure of the Dutch newborn screening program without harming the current newborn screening; (3) assessing the practical and ethical implications of screening only boys for ALD; and (4) setting up a comprehensive follow-up that is both patient- and parent-friendly. We successfully developed and validated a screening algorithm that can be integrated into the Dutch newborn screening program. The core of this algorithm is the “X-counter.” The X-counter determines the number of X chromosomes without assessing the presence of a Y chromosome. The X-counter is integrated as second tier in our 4-tier screening algorithm. Furthermore, we ensured that our screening algorithm does not result in unsolicited findings. Finally, we developed a patient- and parent-friendly, multidisciplinary, centralized follow-up protocol. Our boys-only ALD screening algorithm offers a solution for countries that encounter similar ethical considerations, for ALD as well as for other X-linked diseases. For ALD, this alternative boys-only screening algorithm may result in a more rapid inclusion of ALD in newborn screening programs worldwide.

          Related collections

          Most cited references35

          • Record: found
          • Abstract: found
          • Article: not found

          Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters.

          Adrenoleukodystrophy (ALD) is an X-linked disease affecting 1/20,000 males either as cerebral ALD in childhood or as adrenomyeloneuropathy (AMN) in adults. Childhood ALD is the more severe form, with onset of neurological symptoms between 5-12 years of age. Central nervous system demyelination progresses rapidly and death occurs within a few years. AMN is a milder form of the disease with onset at 15-30 years of age and a more progressive course. Adrenal insufficiency (Addison's disease) may remain the only clinical manifestation of ALD. The principal biochemical abnormality of ALD is the accumulation of very-long-chain fatty acids (VLCFA) because of impaired beta-oxidation in peroxisomes. The normal oxidation of VLCFA-CoA in patients' fibroblasts suggested that the gene coding for the VLCFA-CoA synthetase could be a candidate gene for ALD. Here we use positional cloning to identify a gene partially deleted in 6 of 85 independent patients with ALD. In familial cases, the deletions segregated with the disease. An identical deletion was detected in two brothers presenting with different clinical ALD phenotypes. Candidate exons were identified by computer analysis of genomic sequences and used to isolate complementary DNAs by exon connection and screening of cDNA libraries. The deduced protein sequence shows significant sequence identity to a peroxisomal membrane protein of M(r) 70K that is involved in peroxisome biogenesis and belongs to the 'ATP-binding cassette' superfamily of transporters.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Revisiting Wilson and Jungner in the genomic age: a review of screening criteria over the past 40 years.

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              X-linked adrenoleukodystrophy.

              X-linked adrenoleukodystrophy (X-ALD) is caused by a defect in the gene ABCD1, which maps to Xq28 and codes for a peroxisomal membrane protein that is a member of the ATP-binding cassette transporter superfamily. X-ALD is panethnic and affects approximately 1:20,000 males. Phenotypes include the rapidly progressive childhood, adolescent, and adult cerebral forms; adrenomyeloneuropathy, which presents as slowly progressive paraparesis in adults; and Addison disease without neurologic manifestations. These phenotypes are frequently misdiagnosed, respectively, as attention-deficit hyperactivity disorder (ADHD), multiple sclerosis, or idiopathic Addison disease. Approximately 50% of female carriers develop a spastic paraparesis secondary to myelopathic changes similar to adrenomyeloneuropathy. Assays of very long chain fatty acids in plasma, cultured chorion villus cells and amniocytes, and mutation analysis permit presymptomatic and prenatal diagnosis, as well as carrier identification. The timely use of these assays is essential for genetic counseling and therapy. Early diagnosis and treatment can prevent overt Addison disease, and significantly reduce the frequency of the severe childhood cerebral phenotype. A promising new method for mass newborn screening has been developed, the implementation of which will have a profound effect on the diagnosis and therapy of X-ALD.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                17 June 2020
                2020
                : 8
                : 499
                Affiliations
                [1] 1Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam UMC, Amsterdam Gastroenterology and Metabolism, University of Amsterdam , Amsterdam, Netherlands
                [2] 2Pediatric Metabolic Diseases, Amsterdam UMC, Emma Children’s Hospital, University of Amsterdam , Amsterdam, Netherlands
                [3] 3Centre for Health Protection, National Institute for Public Health and the Environment (RIVM) , Bilthoven, Netherlands
                [4] 4Department of Clinical Genetics, Amsterdam UMC, Amsterdam Reproduction & Development, University of Amsterdam , Amsterdam, Netherlands
                [5] 5Department of Clinical Chemistry, Neonatal Screening Laboratory, Endocrine Laboratory, Amsterdam UMC, Amsterdam Gastroenterology and Metabolism, University of Amsterdam , Amsterdam, Netherlands
                [6] 6Reference Laboratory for Neonatal Screening, Centre for Health Protection, National Institute for Public Health and the Environment (RIVM) , Bilthoven, Netherlands
                [7] 7Centre for Population Screening, National Institute for Public Health and the Environment (RIVM) , Bilthoven, Netherlands
                [8] 8Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam UMC, Amsterdam Gastroenterology and Metabolism, Vrije Universiteit Amsterdam , Amsterdam, Netherlands
                [9] 9Department for Vaccine Supply and Prevention Programmes, National Institute for Public Health and the Environment (RIVM) , Bilthoven, Netherlands
                [10] 10Department of Pediatric Endocrinology, Amsterdam UMC, Emma Children’s Hospital, University of Amsterdam , Amsterdam, Netherlands
                [11] 11Department of Pediatric Neurology, Amsterdam UMC, Amsterdam Leukodystrophy Center, Emma Children’s Hospital, Amsterdam Neuroscience, University of Amsterdam , Amsterdam, Netherlands
                Author notes

                Edited by: Maya Schuldiner, Weizmann Institute of Science, Israel

                Reviewed by: Joseph J. Orsini, New York State Department of Health, United States; Carine De Marcos Lousa, Leeds Beckett University, United Kingdom

                *Correspondence: Stephan Kemp, s.kemp@ 123456amsterdamumc.nl

                This article was submitted to Membrane Traffic, a section of the journal Frontiers in Cell and Developmental Biology

                Article
                10.3389/fcell.2020.00499
                7311642
                32626714
                059e3943-7de7-4dd8-a2e6-bb6d2bac240b
                Copyright © 2020 Barendsen, Dijkstra, Visser, Alders, Bliek, Boelen, Bouva, van der Crabben, Elsinghorst, van Gorp, Heijboer, Jansen, Jaspers, van Lenthe, Metgod, Mooij, van der Sluijs, van Trotsenburg, Verschoof-Puite, Vaz, Waterham, Wijburg, Engelen, Dekkers and Kemp.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 08 April 2020
                : 25 May 2020
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 44, Pages: 12, Words: 0
                Funding
                Funded by: ZonMw 10.13039/501100001826
                Award ID: 543002004
                Categories
                Cell and Developmental Biology
                Original Research

                adrenoleukodystrophy,peroxisomes,newborn screening,neonatal,gender,heel prick,dried bloodspots,x chromosome

                Comments

                Comment on this article