Adrenoleukodystrophy Newborn Screening in California Since 2016: Programmatic Outcomes and Follow-Up.
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ABSTRACT:
SUBMITTER: Matteson J
PROVIDER: S-EPMC8167547 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo conduct interviews with a multiyear sample of parents of infants found to have heterozygous status for sickle cell hemoglobinopathy or cystic fibrosis during newborn blood screening (NBS).Study designInterviewers with clinical backgrounds telephoned parents, and followed a structured script that blended follow-up and research purposes. Recruiting followed several steps to minimize recruiting bias as much as possible for a NBS study.ResultsFollow-up calls were conducted with parents of 426 infant carriers of sickle cell hemoglobinopathy, and 288 parents of cystic fibrosis carriers (34.8% and 49.6% of those eligible). Among these, 27.5% and 7.8% had no recollection of being informed of NBS results. Of those who recalled a provider explanation, 8.6% and 13.0% appraised the explanation negatively. Overall, 7.4% and 13.2% were dissatisfied with the experience of learning about the NSB result. Mean anxiety levels were low but higher in the sickle cell hemoglobinopathy group (P < .001). Misconceptions that the infant might get the disease were present in 27.5% and 7.8% of parents (despite zero actual risk for disease). Several of these data were significantly predicted by NBS result, health literacy, parental age, and race/ethnicity factors.ConclusionsPatient-centered public health follow-up can be effective after NBS identifies carrier status. Psychosocial complications were uncommon, but harms were substantial enough to justify mitigation.
| S-EPMC7483722 | biostudies-literature
Project description:Background:Newborn screening (NBS) programs for treatable metabolic disorders have been enormously successful, but molecular-based screening has not been broadly implemented so far. Methods:This prospective pilot study was performed within the German NBS framework. DNA, extracted from dried blood cards was collected as part of the regular NBS program. As cystinosis has a prevalence of only 1:100,000-1:200,000, a molecular genetic assay for detection of the SMN1 gene mutation with a higher prevalence was also included in the screening process, a genetic defect that leads to spinal muscular atrophy (SMA). First tier multiplex PCR was employed for both diseases. The cystinosis screening employed assays for the three most common CTNS mutations covering 75% of German patients; in case of heterozygosity for one of these mutations, samples were screened by next generation sequencing (NGS) of the CTNS exons for 101 CTNS mutations. A detection rate of 98.5% is predicted using this approach. Results:Between January 15, 2018 and May 31, 2019, 257,734 newborns were screened in Germany for cystinosis. One neonate was diagnosed with cystinosis, consistent with the known incidence of the disease. No false positive or false negatives were detected so far. Screening, communication of findings to parents, and confirmation of diagnosis were accomplished in a multi-disciplinary setting. This program was accomplished with the cooperation of hospitals, physicians, and parents. In the neonate diagnosed with cystinosis, oral cysteamine treatment began on day 18. After 16?months of treatment the child has no clinical signs of renal tubular Fanconi syndrome. Conclusions:This pilot study demonstrates the efficacy of a molecular-based neonatal screening program for cystinosis using an existing national screening framework.
| S-EPMC6796768 | biostudies-literature
Project description:Males with X-linked adrenoleukodystrophy (ALD) are at high risk for developing adrenal insufficiency and/or progressive leukodystrophy (cerebral ALD) at an early age. Pathogenic variants in ABCD1 result in elevated levels of very long-chain fatty acids (VLCFA), including C26:0-lysophosphatidylcholine (C26:0-LPC). Newborn screening for ALD enables prospective monitoring and timely therapeutic intervention, thereby preventing irreversible damage and saving lives. The Dutch Health Council recommended to screen only male newborns for ALD without identifying untreatable conditions associated with elevated C26:0-LPC, like Zellweger spectrum disorders and single peroxisomal enzyme defects. Here, we present the results of the SCAN (Screening for ALD in the Netherlands) study which is the first sex-specific newborn screening program worldwide. Males with ALD are identified based on elevated C26:0-LPC levels, the presence of one X-chromosome and a variant in ABCD1, in heel prick dried bloodspots. Screening of 71 208 newborns resulted in the identification of four boys with ALD who, following referral to the pediatric neurologist and confirmation of the diagnosis, enrolled in a long-term follow-up program. The results of this pilot show the feasibility of employing a boys-only screening algorithm that identifies males with ALD without identifying untreatable conditions. This approach will be of interest to countries that are considering ALD newborn screening but are reluctant to identify girls with ALD because for girls there is no direct health benefit. We also analyzed whether gestational age, sex, birth weight and age at heel prick blood sampling affect C26:0-LPC concentrations and demonstrate that these covariates have a minimal effect.
| S-EPMC10092852 | biostudies-literature
Project description:Newborn screening (NBS) follow-up programs in the United States are managed at the state level, leaving limited opportunities for collaboration across programs and coordinated resource sharing. The Newborn Screening Technical assistance and Evaluation Program (NewSTEPs), a program of the Association of Public Health Laboratories (APHL), has established a national community of practice for NBS follow-up by creating a network of follow-up staff and stakeholders through education and engagement opportunities. The activities of NewSTEPs in support of NBS follow-up have strengthened information dissemination, collaboration, data collection and technical assistance-driven mentorship across the national system.
| S-EPMC8395728 | biostudies-literature
Project description:Importance:X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal genetic disorder in which an accumulation of very long-chain fatty acids leads to inflammatory demyelination in the central nervous system and to adrenal cortex atrophy. In 2016, X-ALD was added to the US Recommended Uniform Screening Panel. Objective:To evaluate the performance of a single-tier newborn screening assay for X-ALD in North Carolina. Design, Setting, and Participants:This diagnostic screening study was of all newborn dried blood spot specimens received in the North Carolina State Laboratory of Public Health between January 2 and June 1, 2018, excluding specimens of insufficient quantity or quality. A total of 52?301 specimens were screened for X-ALD using negative ionization high-performance liquid chromatography tandem mass spectrometry to measure C24:0- and C26:0-lysophosphatidylcholine concentrations. Sanger sequencing of the adenosine triphosphate-binding cassette subfamily D member 1 (ABCD1) gene was performed on screen-positive specimens. Exposures:A medical and family history, newborn physical examination, sequencing of ABCD1 on dried blood spot samples, and plasma analysis of very long-chain fatty acids were obtained for all infants with screen-positive results. Main Outcomes and Measures:The prevalence of X-ALD in North Carolina and the positive predictive value and false-positive rate for the first-tier assay were determined. Results:Of 52?301 infants tested (47.8% female, 50.6% male, and 1.7% other or unknown sex), 12 received screen-positive results. Of these 12 infants, 8 were confirmed with a genetic disorder: 3 male infants with X-ALD, 3 X-ALD-heterozygous female infants, 1 female infant with a peroxisome biogenesis disorder, and 1 female infant with Aicardi-Goutières syndrome. Four infants were initially classified as having false-positives results, including 3 female infants who were deemed unaffected and 1 male infant with indeterminate results on confirmatory testing. The positive predictive value for X-ALD or other genetic disorders for the first-tier assay was 67%, with a false-positive rate of 0.0057%. Conclusions and Relevance:This newborn screening pilot study reported results on 2 lysophosphatidylcholine analytes, identifying 3 male infants with X-ALD, 3 X-ALD-heterozygous female infants, and 3 infants with other disorders associated with increased very long-chain fatty acids. These results showed successful implementation in a public health program with minimal risk to the population. The findings will support other state laboratories planning to implement newborn screening for X-ALD and related disorders.
| S-EPMC7042889 | biostudies-literature
Project description:Adrenoleukodystrophy (ALD) is a rare X-linked disease caused by a mutation of the peroxisomal ABCD1 gene. This review summarizes our current understanding of the pathogenic cell- and tissue-specific roles of lipid species in the context of experimental therapeutic strategies and provides an overview of critical historical developments, therapeutic trials and the advent of newborn screening in the USA. In ALD, very long-chain fatty acid (VLCFA) chain length-dependent dysregulation of endoplasmic reticulum stress and mitochondrial radical generating systems inducing cell death pathways has been shown, providing the rationale for therapeutic moiety-specific VLCFA reduction and antioxidant strategies. The continuing increase in newborn screening programs and promising results from ongoing and recent therapeutic investigations provide hope for ALD.
| S-EPMC7041623 | biostudies-literature
Project description:AbstractOne in 120 children are born with sickle cell disease (SCD) in Haiti. However, health care challenges include isolated newborn screening (NBS) activities and lack of transcranial Doppler (TCD) ultrasound to assess stroke risk. The implementation activities of the Comparative Study of Children in Haiti and Miami with Sickle Cell Disease involved both NBS and TCD ultrasound implementations at 4 Haitian clinical sites. We hypothesized that hospital-based newborn SCD screening and follow-up programs would be feasible at Haiti. A traditional NBS laboratory method with dried blood samples was performed at 3 Port-au-Prince sites, and the traditional method plus point-of-care (POC) testing was used at the 2 northern sites. The rate of clinical follow-up for newborns with SCD as the outcome for the NBS intervention was compared with that of the NBS method. The NBS programs identified SCD in 0.77% of 8224 newborns over a 24-month period. In the rural hospital assigned to the combination screening, 56% of newborns identified with POC testing returned for follow-up, compared with 0% when POC was not available (P = .044). Newborns who tested positive for SCD and children aged <6 years with SCD at the clinical sites were eligible for study follow-up. Accrual was successful: 165 participants (mean age, 42 months; 53% males; 93% hemoglobin SS) were recruited and received oral penicillin. TCD ultrasound screening was hampered by poor internet connections and trained staff leaving Haiti, with only 1 active site conducting screening. Despite challenges, the implementation of NBS and sickle cell programs in Haiti is feasible. We are in the process of understanding how to mitigate implementation limitations.
| S-EPMC10784669 | biostudies-literature
Project description:The secretary of the US Department of Health and Human Services in February 2016 recommended that X-linked adrenoleukodystrophy (X-ALD) be added to the recommended uniform screening panel for state newborn screening programs. This decision was informed by data presented on the accuracy of screening from New York, the only state that currently offers X-ALD newborn screening, and published and unpublished data showing health benefits of earlier treatment (hematopoietic stem cell transplantation and adrenal hormone replacement therapy) for the childhood cerebral form of X-ALD. X-ALD newborn screening also identifies individuals with later-onset disease, but poor genotype-phenotype correlation makes predicting health outcomes difficult and might increase the risk of unnecessary treatment. Few data are available regarding the harms of screening and presymptomatic identification. Significant challenges exist for implementing comprehensive X-ALD newborn screening, including incorporation of the test, coordinating follow-up diagnostic and treatment care, and coordination of extended family testing after case identification.Genet Med 19 1, 121-126.
| S-EPMC5182180 | biostudies-literature
Project description:BackgroundA decision tree model was built to estimate the economic impact of introducing screening for X-linked adrenoleukodystrophy (X-ALD) into an existing tandem mass spectrometry based newborn screening programme. The model was based upon the UK National Health Service (NHS) Newborn Blood Spot Screening Programme and a public service perspective was used with a lifetime horizon. The model structure and parameterisation were based upon literature reviews and expert clinical judgment. Outcomes included health, social care and education costs and quality adjusted life years (QALYs). The model assessed screening of boys only and evaluated the impact of improved outcomes from hematopoietic stem cell transplantation in patients with cerebral childhood X-ALD (CCALD). Threshold analyses were used to examine the potential impact of utility decrements for non-CCALD patients identified by screening.ResultsIt is estimated that screening 780,000 newborns annually will identify 18 (95%CI 12, 27) boys with X-ALD, of whom 10 (95% CI 6, 15) will develop CCALD. It is estimated that screening may detect 7 (95% CI 3, 12) children with other peroxisomal disorders who may also have arisen symptomatically. If results for girls are returned an additional 17 (95% CI 12, 25) cases of X-ALD will be identified. The programme is estimated to cost an additional £402,000 (95% CI £399-407,000) with savings in lifetime health, social care and education costs leading to an overall discounted cost saving of £3.04 (95% CI £5.69, £1.19) million per year. Patients with CCALD are estimated to gain 8.5 discounted QALYs each giving an overall programme benefit of 82 (95% CI 43, 139) QALYs.ConclusionIncluding screening of boys for X-ALD into an existing tandem mass spectrometry based newborn screening programme is projected to reduce lifetime costs and improve outcomes for those with CCALD. The potential disbenefit to those identified with non-CCALD conditions would need to be substantial in order to outweigh the benefit to those with CCALD. Further evidence is required on the potential QALY impact of early diagnosis both for non-CCALD X-ALD and other peroxisomal disorders. The favourable economic results are driven by estimated reductions in the social care and education costs.
| S-EPMC6182830 | biostudies-literature
Project description:BACKGROUND:Mucopolysaccharidoses (MPS) are lysosomal storage diseases in which mutations of genes encoding for lysosomal enzymes cause defects in the degradation of glycosaminoglycans (GAGs). The accumulation of GAGs in lysosomes results in cellular dysfunction and clinical abnormalities. The early initiation of enzyme replacement therapy (ERT) can slow or prevent the development of severe clinical manifestations. MPS I and II newborn screening has been available in Taiwan since August 2015. Infants who failed the recheck at recall were referred to MacKay Memorial Hospital for a detailed confirmatory diagnosis. METHODS:From August 2015 to November 2017, 294,196 and 153,032 infants were screened using tandem mass spectrometry for MPS I and MPS II, respectively. Of these infants, 84 suspected cases (eight for MPS I; 76 for MPS II) were referred for confirmation. Urinary first-line biochemistry examinations were performed first, including urinary GAG quantification, two-dimensional electrophoresis, and tandem mass spectrometry assay for predominant disaccharides derived from GAGs. If the results were positive, a confirmative diagnosis was made according to the results of leukocyte enzymatic assay and molecular DNA analysis. Leukocyte pellets were isolated from EDTA blood and used for fluorescent ?-iduronidase (IDUA) or iduronate-2-sulfatase (IDS) enzymatic assay. DNA sequencing analysis was also performed. RESULTS:Normal IDS and IDUA enzyme activities were found in most of the referred cases except for four who were strongly suspected of having MPS I and three who were strongly suspected of having MPS II. Of these infants, three with novel mutations of the IDS gene (c.817C?>?T, c.1025A?>?G, and c.311A?>?T) and four with two missense mutations of the IDUA gene (C.300-3C?>?G, c.1874A?>?C; c.1037 T?>?G, c.1091C?>?T) showed significant deficiencies in IDS and IDUA enzyme activities (<?5% of mean normal activity), respectively. Urinary dermatan sulfate and heparan sulfate quantitative analyses by tandem mass spectrometry also demonstrated significant elevations. The prevalence rates of MPS I and MPS II in Taiwan were 1.35 and 1.96 per 100,000 live births, respectively. CONCLUSIONS:The early initiation of ERT for MPS can result in better clinical outcomes. An early confirmatory diagnosis increases the probability of receiving appropriate medical care such as ERT quickly enough to avoid irreversible manifestations. All high risk infants identified in this study so far remain asymptomatic and are presumed to be affected with the attenuated disease variants.
| S-EPMC5970538 | biostudies-literature