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Magalhães NNS, Mathiasi LB, Werneck Rodrigues DDO. Importance of neonatal screening: A case study of sickle cell disease and cystic fibrosis coexistence. World J Clin Pediatr 2025; 14:97537. [DOI: 10.5409/wjcp.v14.i1.97537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 09/10/2024] [Accepted: 09/30/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Neonatal screening (NS) is a public health policy to identify genetic pathologies such as cystic fibrosis (CF), sickle cell disease, and other diseases. Sickle cell disease is the comprehensive term for a group of hemoglobinopathies characterized by the presence of hemoglobin S. CF is an autosomal recessive multisystemic disease with pathophysiology involving deleterious mutations in the transmembrane regulatory gene that encodes a protein that regulates the activity of chloride and sodium channels in the cell surface epithelium. NS is crucial for early diagnosis and management, which ensures a better quality of life.
AIM To report a case of the coexistence of sickle cell anemia (SCA) and CF and perform an integrative literature review.
METHODS This is an observational study and a review of the literature focusing on two rare genetic pathologies identified simultaneously in NS from the perspective of a clinical case. The authors identified only 5 cases of SCA associated with CF. No clinical trials or review articles were identified considering the rarity of the coexistence of these two pathologies.
RESULTS Herein, the authors reported the case of a girl who after undergoing NS on day 8 of life was diagnosed with SCA with an alteration in the dosage of immunoreactive trypsin. The diagnosis of CF was confirmed by the Coulometry Sweat Test. The rarity of the co-occurrence of these two severe genetic pathologies (CF and SCA) is a challenge for medical science.
CONCLUSION This study adds to the few case reports present in the literature that highlight the identification of two severe diseases via NS.
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Affiliation(s)
| | - Lucas Barra Mathiasi
- Department of Internal Medicine, Rede D'Or Rio de Janeiro, Rio de Janeiro 22270-010, Brazil
| | - Daniela de Oliveira Werneck Rodrigues
- Department of Hematology, Fundação Hemominas, Juiz de Fora 36010-560, MG, Brazil
- Department of Internal Medicine, Universidade Presidente Antônio Carlos - Faculdade de Medicina Juiz de Fora, Juiz de Fora 36010-560, Minas Gerais, Brazil
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Tinggaard J, Pedersen SV, Larsen ML, Jensen AK, Greisen G, Hansen BM, Hoei-Hansen CE. The risk of epilepsy after neonatal seizures. Dev Med Child Neurol 2025. [PMID: 39967409 DOI: 10.1111/dmcn.16255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 12/22/2024] [Accepted: 01/09/2025] [Indexed: 02/20/2025]
Abstract
AIM To estimate the cumulative risk of epilepsy after neonatal seizures and identify subpopulations at increased risk. METHOD This was a nationwide register-based cohort study including all children born in Denmark between 1997 and 2018. The cumulative risk of epilepsy in children with and without neonatal seizures was compared. Furthermore, neonatal seizures were stratified according to aetiology. RESULTS We followed 1 294 377 children and identified 1998 neonatal survivors with neonatal seizures. The cumulative risk of epilepsy was 20.4% (95% confidence interval [CI] = 18.5-22.3) among children with neonatal seizures, compared to 1.15% (95% CI = 1.12-1.18) among children without. Epilepsy was diagnosed before 1 year of age in 11.4% of children with neonatal seizures, in an additional 4.5% between 1 year and 5 years, 3.1% between 5 years and 10 years, and 1.4% between 10 years and 22 years. The aetiologies of neonatal cerebral infarction, haemorrhage, or malformations (adjusted hazard ratio = 2.49, 95% CI = 1.98-3.14) and low Apgar score (1.49, 95% CI = 1.12-1.98) were associated with the highest risk of epilepsy, compared to children with seizures of unknown aetiology. INTERPRETATION Epilepsy after neonatal seizures is common and remains a substantial risk throughout childhood. Aetiological risk factors are identifiable and relevant when planning appropriate information for parents and follow-up.
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Affiliation(s)
- Jeanette Tinggaard
- Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Signe V Pedersen
- Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Mads L Larsen
- Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Andreas K Jensen
- Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark
| | - Gorm Greisen
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Neonatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Bo M Hansen
- Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Hilleroed, Denmark
| | - Christina E Hoei-Hansen
- Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Therrell BL, Padilla CD, Borrajo GJC, Khneisser I, Schielen PCJI, Knight-Madden J, Malherbe HL, Kase M. Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020-2023). Int J Neonatal Screen 2024; 10:38. [PMID: 38920845 PMCID: PMC11203842 DOI: 10.3390/ijns10020038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 03/28/2024] [Accepted: 03/28/2024] [Indexed: 06/27/2024] Open
Abstract
Newborn bloodspot screening (NBS) began in the early 1960s based on the work of Dr. Robert "Bob" Guthrie in Buffalo, NY, USA. His development of a screening test for phenylketonuria on blood absorbed onto a special filter paper and transported to a remote testing laboratory began it all. Expansion of NBS to large numbers of asymptomatic congenital conditions flourishes in many settings while it has not yet been realized in others. The need for NBS as an efficient and effective public health prevention strategy that contributes to lowered morbidity and mortality wherever it is sustained is well known in the medical field but not necessarily by political policy makers. Acknowledging the value of national NBS reports published in 2007, the authors collaborated to create a worldwide NBS update in 2015. In a continuing attempt to review the progress of NBS globally, and to move towards a more harmonized and equitable screening system, we have updated our 2015 report with information available at the beginning of 2024. Reports on sub-Saharan Africa and the Caribbean, missing in 2015, have been included. Tables popular in the previous report have been updated with an eye towards harmonized comparisons. To emphasize areas needing attention globally, we have used regional tables containing similar listings of conditions screened, numbers of screening laboratories, and time at which specimen collection is recommended. Discussions are limited to bloodspot screening.
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Affiliation(s)
- Bradford L. Therrell
- Department of Pediatrics, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA
- National Newborn Screening and Global Resource Center, Austin, TX 78759, USA
| | - Carmencita D. Padilla
- Department of Pediatrics, College of Medicine, University of the Philippines Manila, Manila 1000, Philippines;
| | - Gustavo J. C. Borrajo
- Detección de Errores Congénitos—Fundación Bioquímica Argentina, La Plata 1908, Argentina;
| | - Issam Khneisser
- Jacques LOISELET Genetic and Genomic Medical Center, Faculty of Medicine, Saint Joseph University, Beirut 1104 2020, Lebanon;
| | - Peter C. J. I. Schielen
- Office of the International Society for Neonatal Screening, Reigerskamp 273, 3607 HP Maarssen, The Netherlands;
| | - Jennifer Knight-Madden
- Caribbean Institute for Health Research—Sickle Cell Unit, The University of the West Indies, Mona, Kingston 7, Jamaica;
| | - Helen L. Malherbe
- Centre for Human Metabolomics, North-West University, Potchefstroom 2531, South Africa;
- Rare Diseases South Africa NPC, The Station Office, Bryanston, Sandton 2021, South Africa
| | - Marika Kase
- Strategic Initiatives Reproductive Health, Revvity, PL10, 10101 Turku, Finland;
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Groden CM, Vetter CJ, Salih ZNI. Parental Experiences of Genetic Testing. Neoreviews 2024; 25:e151-e158. [PMID: 38425197 DOI: 10.1542/neo.25-3-e151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2024]
Abstract
Genetic testing is increasingly used in clinical practice in the neonatal period, including in NICUs. This testing may have psychological consequences for parents. To best support families, neonatal clinicians should be aware of the various ways in which parents view and respond to genetic testing. In this review, we summarize research on the parental experience of having a newborn infant undergo genetic testing.
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Affiliation(s)
| | - Cecelia J Vetter
- Ruth Lily Medical Library, Indiana University School of Medicine, Indianapolis, IN
| | - Zeynep N I Salih
- Division of Neonatal-Perinatal Medicine, Indiana University School of Medicine, Indianapolis, IN
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Sobotka SA, Ross LF. Newborn Screening for Neurodevelopmental Disorders May Exacerbate Health Disparities. Pediatrics 2023; 152:e2023061727. [PMID: 37727945 PMCID: PMC10522928 DOI: 10.1542/peds.2023-061727] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/12/2023] [Indexed: 09/21/2023] Open
Abstract
Newborn screening (NBS) began in the early 1960s with screening for phenylketonuria on blood collected on filter paper. The number of conditions included in NBS programs expanded significantly with the adoption of tandem mass spectrometry. The recommended uniform screening panel provides national guidance and has reduced state variability. Universality and uniformity have been supported to promote equity. Recently, a number of researchers have suggested expanding NBS to include genomic sequencing to identify all genetic disorders in newborns. This has been specifically suggested for genes that increase the risk for neurodevelopmental disorders (NDDs), with the presumption that early identification in the newborn period would reduce disabilities. We offer arguments to show that genomic sequencing of newborns for NDDs risks exacerbating disparities. First, the diagnosis of NDD requires clinical expertise, and both genetic and neurodevelopmental expertise are in short supply, leading to disparities in access to timely follow-up. Second, therapies for children with NDDs are insufficient to meet their needs. Increasing early identification for those at risk who may never manifest developmental delays could shift limited resources to those children whose parents are more poised to advocate, worsening disparities in access to services. Rather, we suggest an alternative: genomic sequencing of all children with diagnosed NDDs. This focused strategy would have the potential to target genomic sequencing at children who manifest NDDs across diverse populations which could better improve our understanding of contributory genes to NDDs.
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Affiliation(s)
- Sarah A. Sobotka
- Section of Developmental and Behavioral Pediatrics, Department of Pediatrics, The University of Chicago, Chicago, Illinois
| | - Lainie Friedman Ross
- Department of Health Humanities; and Bioethics
- Paul M Schyve, MD Center for Bioethics, University of Rochester School of Medicine and Dentistry, Rochester, New York
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DeCelie-Germana JK, Bonitz L, Langfelder-Schwind E, Kier C, Diener BL, Berdella M. Diagnostic and Communication Challenges in Cystic Fibrosis Newborn Screening. Life (Basel) 2023; 13:1646. [PMID: 37629501 PMCID: PMC10455801 DOI: 10.3390/life13081646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 07/14/2023] [Accepted: 07/25/2023] [Indexed: 08/27/2023] Open
Abstract
As of December 2009, cystic fibrosis (CF) newborn screening (NBS) is performed in all 50 US states and the District of Columbia. Widespread implementation of CF newborn screening (CFNBS) in the US and internationally has brought about new and varied challenges. Immunoreactive trypsinogen (IRT) remains the first, albeit imperfect, biomarker used universally in the screening process. Advances in genetic testing have provided an opportunity for newborn screening programs to add CFTR sequencing tiers to their algorithms. This in turn will enable earlier identification of babies with CF and improve longer-term outcomes through prompt treatment and intervention. CFTR sequencing has led to the ability to identify infants with CF from diverse ethnic and racial backgrounds more equitably while also identifying an increasing proportion of infants with inconclusive diagnoses. Using the evolution of the New York State CF newborn screening program as a guide, this review outlines the basic steps in a universal CF newborn screening program, considers how to reduce bias, highlights challenges, offers guidance to address these challenges and provides recommendations for future consideration.
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Affiliation(s)
- Joan Kathleen DeCelie-Germana
- Cohen Children’s Medical Center, Division of Pediatric Pulmonary and Cystic Fibrosis, Zucker School of Medicine at Hofstra/Northwell, New York, NY 11040, USA;
| | - Lynn Bonitz
- Cohen Children’s Medical Center, Division of Pediatric Pulmonary and Cystic Fibrosis, Zucker School of Medicine at Hofstra/Northwell, New York, NY 11040, USA;
| | - Elinor Langfelder-Schwind
- The Cystic Fibrosis Center, Department of Pulmonary Medicine, Lenox Hill Hospital, Northwell Health, New York, NY 10075, USA; (E.L.-S.); (M.B.)
| | - Catherine Kier
- Department of Pediatrics, Renaissance School of Medicine at Stony Brook, Stony Brook, New York, NY 11794, USA; (C.K.); (B.L.D.)
| | - Barry Lawrence Diener
- Department of Pediatrics, Renaissance School of Medicine at Stony Brook, Stony Brook, New York, NY 11794, USA; (C.K.); (B.L.D.)
| | - Maria Berdella
- The Cystic Fibrosis Center, Department of Pulmonary Medicine, Lenox Hill Hospital, Northwell Health, New York, NY 10075, USA; (E.L.-S.); (M.B.)
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Octavius GS, Daleni VA, Sagala YDS. An Insight into Indonesia's Challenges in Implementing Newborn Screening Programs and Their Future Implications. CHILDREN (BASEL, SWITZERLAND) 2023; 10:1216. [PMID: 37508713 PMCID: PMC10378005 DOI: 10.3390/children10071216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 07/04/2023] [Accepted: 07/12/2023] [Indexed: 07/30/2023]
Abstract
Due to high entry barriers, countries might find it daunting to implement the NBS program, especially those just trying to start it. This review aims to discuss Indonesia's barriers that hinder newborn screening (NBS) implementation while discussing the future implications. Literature in Pubmed and Google Scholar was scoured with keywords such as "Newborn Screening", "Neonatal Screening", "Indonesia", "Asia Pacific", "Barriers", and "Challenges". We also searched for relevant references in those published articles. Grey literature, such as state regulations, informative webinars on the topics by experts regarding current situations, and press releases by the Indonesian Minister of Health (MoH), was also searched. Newborn screening is no longer considered just a laboratory test but an array of well-harmonized systems that must be orchestrated well. Some of the barriers Indonesia faces in implementing NBS are a lack of prevalence data, ethical issues, infrastructure, cost-benefit analysis, logistical issues, government support, patient issues, a lack of commitments, and a lack of healthcare workers, specialization, and training. Government support with professional advocates and support groups, proper infrastructure, and a single-payer system for NBS programs are necessary to accelerate NBS programs in Indonesia.
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Affiliation(s)
- Gilbert Sterling Octavius
- Department of Pediatrics, Universitas Pelita Harapan, Tangerang 15811, Indonesia
- St. Theresia Hospital, Jambi 36123, Indonesia
| | - Vamela Adman Daleni
- Department of Pediatrics, Universitas Pelita Harapan, Tangerang 15811, Indonesia
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Pinto VM, De Franceschi L, Gianesin B, Gigante A, Graziadei G, Lombardini L, Palazzi G, Quota A, Russo R, Sainati L, Venturelli D, Forni GL, Origa R. Management of the Sickle Cell Trait: An Opinion by Expert Panel Members. J Clin Med 2023; 12:jcm12103441. [PMID: 37240547 DOI: 10.3390/jcm12103441] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 04/21/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023] Open
Abstract
The number of individuals with the sickle cell trait exceeds 300 million worldwide, making sickle cell disease one of the most common monogenetic diseases globally. Because of the high frequency of sickle cell disease, reproductive counseling is of crucial importance. In addition, unlike other carrier states, Sickle Cell Trait (SCT) seems to be a risk factor for several clinical complications, such as extreme exertional injury, chronic kidney disease, and complications during pregnancy and surgery. This expert panel believes that increasing knowledge about these clinical manifestations and their prevention and management can be a useful tool for all healthcare providers involved in this issue.
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Affiliation(s)
- Valeria Maria Pinto
- Centro della Microcitemia, Anemie Congenite e Dismetabolismo del Ferro, E.O. Ospedali Galliera, 16128 Genova, Italy
| | | | - Barbara Gianesin
- Centro della Microcitemia, Anemie Congenite e Dismetabolismo del Ferro, E.O. Ospedali Galliera, 16128 Genova, Italy
- ForAnemia Foundation, 16124 Genova, Italy
| | - Antonia Gigante
- ForAnemia Foundation, 16124 Genova, Italy
- Società Italiana Talassemie ed Emoglobinopatie (SITE), 09100 Cagliari, Italy
| | - Giovanna Graziadei
- Centro Malattie Rare Internistiche, Medicina Generale, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy
| | - Letizia Lombardini
- Centro Nazionale Trapianti, Istituto Superiore di Sanità, 00161 Roma, Italy
| | - Giovanni Palazzi
- U.O. Oncoematologia Pediatrica, Azienda Ospedaliero-Universitaria di Modena, 41125 Modena, Italy
| | | | - Rodolfo Russo
- Clinica Nefrologica, Dialisi e Trapianto, Dipartimento di Medicina Integrata con il Territorio, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy
| | - Laura Sainati
- Oncoematologia Pediatrica, Azienda Ospedaliera-Università di Padova, 35128 Padova, Italy
| | - Donatella Venturelli
- Servizio Immunotrasfusionale, Azienda Ospedaliero-Universitaria di Modena, 41125 Modena, Italy
| | - Gian Luca Forni
- Centro della Microcitemia, Anemie Congenite e Dismetabolismo del Ferro, E.O. Ospedali Galliera, 16128 Genova, Italy
| | - Raffaella Origa
- Talassemia, Ospedale Pediatrico Microcitemico 'A.Cao', ASL8, Università di Cagliari, 09121 Cagliari, Italy
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Ulph F, Bennett R. Psychological and Ethical Challenges of Introducing Whole Genome Sequencing into Routine Newborn Screening: Lessons Learned from Existing Newborn Screening. New Bioeth 2023; 29:52-74. [PMID: 36181705 DOI: 10.1080/20502877.2022.2124582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
Abstract
As a psychologist and an ethicist, we have explored empirically newborn screening consent and communication processes. In this paper we consider the impact on families if newborn screening uses whole genome sequencing. We frame this within the World Health Organization's definition of health and contend that proposals to use whole genome sequencing in newborn screening take into account the ethical, practical and psychological impact of such screening. We argue that the important psychological processes occurring in the neonatal phase necessitate a clear justification that providing risk information at this stage provides a health benefit. We illustrate how research on current newborn screening can inform whole genome sequencing debates, whilst highlighting important gaps. Obtaining explicit, voluntary, and sufficiently informed consent for newborn screening is challenging, however we stress that such consent is ethically and legally appropriate and psychologically and practically important. We conclude by outling how this might be done.
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Affiliation(s)
- Fiona Ulph
- Division of Psychology & Mental Health, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | - Rebecca Bennett
- Centre for Social Ethics and Policy, Department of Law, School of Social Sciences, Faculty of Humanities, University of Manchester, Manchester, UK
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Sims AM, Cromartie SJ, Gessner L, Campbell A, Coker T, Wang CJ, Tarini BA. Parents' Experiences and Needs Regarding Infant Sickle Cell Trait Results. Pediatrics 2022; 149:e2021053454. [PMID: 35441211 PMCID: PMC9647577 DOI: 10.1542/peds.2021-053454] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/10/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND AND OBJECTIVE Sickle cell trait (SCT) has reproductive implications and can rarely cause health problems. SCT counseling improves parent knowledge but is infrequently received by children with SCT compared with children with cystic fibrosis carrier status. There are no national guidelines on SCT disclosure timing, frequency, or counseling content. Parents' experiences with SCT disclosure and counseling are poorly understood but could inform the development of guidelines. We explored parents' experiences with and desires for SCT disclosure and counseling for their infants with SCT identified via newborn screening. METHODS Parents of infants 2 to 12 months old with SCT were recruited through a state newborn screening program for semistructured interviews to explore their experiences with and desires for SCT disclosure and counseling. Inductive thematic analysis was conducted. RESULTS Sixteen interviews were completed from January to August 2020. Most parents reported that SCT disclosure occurred soon after birth, in person, and by the child's physician. Five themes were identified: parent knowledge before child's SCT disclosure, family planning, the dynamics of SCT disclosure and counseling, emotions and actions after SCT disclosure, and parent desires for the SCT disclosure and counseling process. Two primary parent desires were revealed. Parents want more information about SCT, particularly rare symptomatology, and they want SCT counseling repeated once the child approaches adolescence. CONCLUSION Parents report receiving their child's SCT diagnosis in the early newborn period from their child's doctor but indicate they receive incomplete information. Opportunities exist in primary care pediatrics to better align SCT disclosure timing and counseling content with parent desires.
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Affiliation(s)
- Alexandra M. Sims
- Division of General and Community Pediatrics, Children’s National Hospital, Washington, District of Columbia
- Department of Pediatrics, The George Washington University School of Medicine, Washington, District of Columbia
- Division of General and Community Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | | | - Lelia Gessner
- Division of General and Community Pediatrics, Children’s National Hospital, Washington, District of Columbia
| | - Andrew Campbell
- Department of Pediatrics, The George Washington University School of Medicine, Washington, District of Columbia
- Division of Hematology, Children's National Hospital, Washington, District of Columbia
| | | | - C. Jason Wang
- Departments of Pediatrics and Medicine, Stanford University School of Medicine, Stanford, California
| | - Beth A. Tarini
- Division of General and Community Pediatrics, Children’s National Hospital, Washington, District of Columbia
- Department of Pediatrics, The George Washington University School of Medicine, Washington, District of Columbia
- Children’s National Research, Children’s National Hospital, Washington, District of Columbia
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Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania. Int J Neonatal Screen 2022; 8:ijns8020024. [PMID: 35466195 PMCID: PMC9036281 DOI: 10.3390/ijns8020024] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 03/17/2022] [Accepted: 03/21/2022] [Indexed: 11/24/2022] Open
Abstract
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.
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12
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Jacob SA, Meier ER. Importance of sickle cell trait counseling for adolescents and young adults. Pediatr Blood Cancer 2021; 68:e29300. [PMID: 34399031 PMCID: PMC8965882 DOI: 10.1002/pbc.29300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 07/22/2021] [Accepted: 08/04/2021] [Indexed: 11/07/2022]
Affiliation(s)
- Seethal A. Jacob
- Section of Pediatric Hematology Oncology, Department of Pediatrics, Indiana University, Indianapolis, Indiana, USA,Center for Pediatric and Adolescent Comparative Effectiveness Research, Indiana University, Indianapolis, Indiana, USA
| | - Emily Riehm Meier
- Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana, USA
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Sharma PB, Sathe M, Savant AP. Year in Review 2020: Multisystemic impact of cystic fibrosis. Pediatr Pulmonol 2021; 56:3110-3119. [PMID: 34324789 DOI: 10.1002/ppul.25584] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 07/13/2021] [Accepted: 07/14/2021] [Indexed: 12/13/2022]
Abstract
Clinical care in cystic fibrosis (CF) has continued to advance over the last several years, particularly with the widespread eligibility and use of highly effective modulator therapy. Improved outcomes and longevity of persons with CF (PwCF) have increased recognition of the multisystem impact of the disease on the daily lives of PwCF. This review will cover a broad array of topics, from diagnosis to multisystem effects related to mental health, endocrine, palliative care, reproductive health, otolaryngology, and cardiac issues. Additionally, worldwide care delivery will be reviewed, demonstrating variation in outcomes based on resources and populations served. This review is part of the CF Year in Review 2020 series, focusing on the multi-system effects of CF. This review focuses on articles from Pediatric Pulmonology but also includes articles published in 2020 from other journals that are of particular interest to clinicians.
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Affiliation(s)
- Preeti B Sharma
- Department of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Texas Southwestern and Children's Health, Dallas, Texas, USA
| | - Meghana Sathe
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, University of Texas Southwestern and Children's Health, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Adrienne P Savant
- Department of Pediatrics, Division of Pulmonary Medicine, Tulane University School of Medicine, Children's Hospital of New Orleans, New Orleans, Louisiana, USA
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Farrell PM, Langfelder-Schwind E, Farrell MH. Challenging the dogma of the healthy heterozygote: Implications for newborn screening policies and practices. Mol Genet Metab 2021; 134:8-19. [PMID: 34483044 DOI: 10.1016/j.ymgme.2021.08.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 08/16/2021] [Accepted: 08/17/2021] [Indexed: 10/20/2022]
Abstract
Heterozygous (carrier) status for an autosomal recessive condition is traditionally considered to lack significance for an individual's health, but this assumption has been challenged by a growing body of evidence. Carriers of several autosomal recessive disorders and some X-linked diseases are potentially at risk for the pathology manifest in homozygotes. This minireview provides an overview of the literature regarding health risks to carriers of two common autosomal recessive conditions on the Recommended Uniform Screening Panel: sickle cell disease [sickle cell trait (SCT)] and cystic fibrosis (CF). We also consider and comment on bioethical and policy implications for newborn blood screening (NBS). Health risks for heterozygotes, while relatively low for individuals, are often influenced by intrinsic (e.g., other genomic variants or co-morbidities) and extrinsic (environmental) factors, which present opportunities for personalized genomic medicine and risk counseling. They create a special challenge, however, for developing screening/follow-up policies and for genetic counseling, particularly after identification and reporting of heterozygote status through NBS. Although more research is needed, this minireview of the SCT and CF literature to date leads us to propose that blanket terms such as "healthy heterozygotes" or "unaffected carriers" should be superseded in communications about NBS results, in favor of a more nuanced paradigm of setting expectations for health outcomes with "genotype-to-risk." In the molecular era of NBS, it remains clear that public health needs to become better prepared for the full range of applied genetics.
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Affiliation(s)
- Philip M Farrell
- Departments of Pediatrics and Population Health Sciences, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Clinical Sciences Center (K4/948), Madison, WI 53792, USA.
| | - Elinor Langfelder-Schwind
- The Cystic Fibrosis Center, Mount Sinai Beth Israel, Department of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, 1st Ave at 16th Street, 8F18, New York, NY 10003, USA.
| | - Michael H Farrell
- Departments of Internal Medicine and Pediatrics, University of Minnesota Medical School, Division of General Internal Medicine (MMC 741), 420 Delaware St SE, Minneapolis, MN 55455, USA.
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15
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Williams WA, Ross LF. The Harms of Carrier Status Identification: A Cautionary Warning Against Newborn Sequencing. J Pediatr 2020; 224:22-23. [PMID: 32417254 DOI: 10.1016/j.jpeds.2020.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 05/08/2020] [Indexed: 11/30/2022]
Affiliation(s)
| | - Lainie Friedman Ross
- Department of Pediatrics, MacLean Center for Clinical Medical Ethics, Institute for Translational Medicine, University of Chicago, Chicago, Illinois.
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