Dataset Information

Newborn bloodspot screening for Duchenne muscular dystrophy: 21 years experience in Wales (UK).

ABSTRACT: Duchenne muscular dystrophy (DMD), a progressive X-linked neuromuscular disorder, has an estimated worldwide incidence of 1:3500 male births. Currently, there are no curative treatments and the mean age of diagnosis is 5 years. In addition, subsequent pregnancies frequently occur before a diagnosis is made in an index case. An 'opt in' screening programme was introduced in Wales in 1990 with the aim to: reduce the diagnostic delay, permit reproductive choice and allow planning of the care of the affected boy. Newborn bloodspots were collected routinely as part of the Wales newborn screening programme. Specific consent was obtained for this test separately from the other tests. During the 21-year period, 369,780 bloodspot cards were received from male infants, of these 343,170 (92.8%) were screened using a bloodspot creatine kinase (CK) assay following parental consent. A total of 145 cases had a raised CK activity (≥250 U/l) and at follow-up, at 6-8 weeks of age, 79 cases had a normal serum CK (false-positive rate 0.023%) and 66 cases had an elevated serum CK. DMD was confirmed in 56 cases by genotyping/muscle biopsy studies, Becker muscular dystrophy in 5 cases and other rarer forms of muscular dystrophy in 5 cases. This long-term study has so far identified 13 false-negative cases. The incidence of DMD in Wales of 1:5136 during this period is lower than that of 1:4046 before commencement of screening in Wales. Screening has reduced the diagnostic delay enabling reproductive choice for parents of affected boys and earlier administration of current therapies.

SUBMITTER: Moat SJ

PROVIDER: S-EPMC3778339 | biostudies-other | 2013 Oct

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:BackgroundThe rapidly evolving clinical landscape of Duchenne muscular dystrophy (DMD) is driving innovative approaches for early diagnosis through genomic newborn bloodspot screening (NBS). However, the potential impact of these programs on families and healthcare systems remains unexplored. This study assessed the perceived benefits, harms, barriers, and enablers for DMD NBS amongst primary caregivers of children with DMD and healthcare professionals (HCPs).MethodsThis Australian multi-centre cross-sectional study used a mixed-methods convergent methodology. Participants completed a codeveloped questionnaire and their perceptions on the utility, model of care, and processes of DMD NBS were thematically analysed.FindingsParticipants included 50 caregivers and 26 HCPs (68.5% and 53.1% response rate respectively). Most caregivers (40/50, 80%) perceived net benefits of DMD NBS and highlighted an early diagnosis as actionable knowledge, even with the current paucity of disease modifying therapies. This knowledge was valued to enable access to multidisciplinary supportive care (29/50, 58%), clinical trials (27/50, 54%), psychological support (28/50, 56%), inform reproductive planning (27/50, 54%), and facilitate financial planning based on the future needs of their child (27/50, 54%). Whilst HCPs acknowledged these opportunities, only 16/26 (61.5%) believed there were definite net benefits, with notable concerns over the psychological harms of diagnostic knowledge without a recourse to disease modifying therapeutic intervention early in life.InterpretationCaregivers and HCPs perceived a range of potential benefits of DMD NBS. Health system readiness will be founded on developing an integrated model of care that not only supports the psychosocial and information needs of families receiving a newborn diagnosis of DMD, but also provides care and clinical surveillance for individuals for whom a diagnosis may remain uncertain.FundingMedical Research Futures fund (GNT2017165, MRF2015965).

Project description:Dystrophinopathies cover a spectrum of rare progressive X-linked muscle diseases, arising from DMD mutations. They are among the most common pediatric muscular dystrophies, being Duchenne muscular dystrophy (DMD) the most severe form. Despite the fact that there is still no cure for these serious diseases, unprecedented advances are being made for the development of therapies for DMD. Some of which are already conditionally approved: exon skipping and premature stop codon read-through. The present work aimed to characterize the mutational spectrum of DMD in an Argentinian cohort, to identify candidates for available pharmacogenetic treatments and finally, to conduct a comparative analysis of the Latin American (LA) frequencies of mutations amenable for available DMD therapies. We studied 400 patients with clinical diagnosis of dystrophinopathy, implementing a diagnostic molecular algorithm including: MLPA/PCR/Sanger/Exome and bioinformatics. We also performed a meta-analysis of LA's metrics for DMD available therapies. The employed algorithm resulted effective for the achievement of differential diagnosis, reaching a detection rate of 97%. Because of this, corticosteroid treatment was correctly indicated and validated in 371 patients with genetic confirmation of dystrophinopathy. Also, 20 were eligible for exon skipping of exon 51, 21 for exon 53, 12 for exon 45 and another 70 for premature stop codon read-through therapy. We determined that 87.5% of DMD patients will restore the reading frame with the skipping of only one exon. Regarding nonsense variants, UGA turned out to be the most frequent premature stop codon observed (47%). According to the meta-analysis, only four LA countries (Argentina, Brazil, Colombia and Mexico) provide the complete molecular algorithm for dystrophinopathies. We observed different relations among the available targets for exon skipping in the analyzed populations, but a more even proportion of nonsense variants (∼40%). In conclusion, this manuscript describes the theragnosis carried out in Argentinian dystrophinopathy patients. The implemented molecular algorithm proved to be efficient for the achievement of differential diagnosis, which plays a crucial role in patient management, determination of the standard of care and genetic counseling. Finally, this work contributes with the international efforts to characterize the frequencies and variants in LA, pillars of drug development and theragnosis.

Dataset Information

Newborn bloodspot screening for Duchenne muscular dystrophy: 21 years experience in Wales (UK).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets