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 (Z250 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.

Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management

“…Prevalence of DMD has been reported as 15.9 cases per 100 000 live male births in the USA and 19.5 cases per 100 000 live male births in the UK. 1–3 Progressive muscular damage and degeneration occurs in people with DMD, resulting in muscular weakness, associated motor delays, loss of ambulation, respiratory impairment, and cardiomyopathy. Although the clinical course of skeletal muscle and cardiac involvement can be variable, death usually occurs as a result of cardiac or respiratory compromise.…”

Ethical and Policy Issues in Newborn Screening of Children for Neurologic and Developmental Disorders

“…In Wales, the incidence of DMD dropped from a prescreening rate of 1 in 4046 boys to 1 in 5136 boys, 23 whereas none of the families in Manitoba chose to have prenatal diagnosis. 13 But even if NBS can reduce the number of children born with DMD, it is controversial whether this is a valid goal of NBS, because it reduces the child to his disorder and does not value the unborn child as a whole person.…”

Investigational treatments and therapeutic targets in Becker muscular dystrophy

“…Furthermore, the chances of identifying BMD during the asymptomatic period are increasing through neonatal screening for DMD. Neonatal screening for DMD has been conducted experimentally in some limited regions by determining serum creatine kinase in neonates [78]. Through this screening, not only DMD but also BMD has been identified during the asymptomatic period.…”