News Release

Lysosomal storage disorders more common than thought among children in developed countries raising questions around screening

Peer-Reviewed Publication

The Lancet_DELETED

An analysis of dried blood spots from around 35 000 babies in Austria has shown that lysosomal storage disorders—those in which the lysosome or 'recycling centre' of the body's cells malfunctions—are more common than previously thought. However, they remain rare, raising challenges in both practicality and cost for potential screening. The findings are reported in an Article published Online First by The Lancet, written by Professor Berthold Streubel, Medical University of Vienna, Austria, and colleagues.

Prior to this study, combined incidence of such disorders—that include Gaucher's disease, Pompe's disease, and Fabry's disease— had been estimated at 1 per 7700 livebirths for white people. The advent of electrospray ionisation tandem mass spectrometry (ESI-MS) in 1993 enabled for the first time the identification of several disorders by simultaneous measurement of amino acids and acylcarnitines (another metabolite). Combined with increased technological capacity, this means neonatal screening programmes can now identify a broad range of disorders in which early detection and presymptomatic treatment result in clinical benefit. The recent development of enzyme replacement therapies has further increased interest in this field. A further and more controversial benefit of such expanded programmes is the opportunity to inform parents of future reproductive risks (ie, the risk of having children with similar disorders).

Progressive lysosomal substrate deposition can occur in cells throughout the body and results in gradual deterioration of renal function to end-stage renal disease, cerebrovascular, cardiovascular, or neurological disease; muscle weakness; and cardiomyopathy among other conditions.

In this study, specimens from dried blood spots of 34 736 newborn babies were collected consecutively from January, 2010 to July, 2010, as part of the national routine Austrian newborn screening programme. Anonymised samples were analysed for enzyme activity that indicated a lysosomal storage disorder.

All 34 736 samples were analysed, and low enzyme activities were detected in 38 babies. Mutation analysis confirmed lysosomal storage disorders in 15 of them. The most frequent mutations were found for Fabry's disease (1 per 3859 births), followed by Pompe's disease (1 per 8684), and Gaucher's disease (1 per 17 368). The combined incidence was, at 1 per 2315 births, higher than expected. The mutation spectrum suggested a high number of late-onset diseases.

Three US states have passed legislation to include several lysosomal storage disorders in their neonatal screening programmes in the near future, and Washington State is doing a pilot study to detect Pompe's disease, Fabry's disease, and mucopolysaccharidosis type I. In Europe, the regional neonatal screening programme in Florence, Italy, will start in 2011.

The authors say that neonatal screening programmes are generally intended to identify babies with disorders in which early detection and urgent presymptomatic treatment are necessary to avert serious clinical harm. They say their study shows that it is technical feasible to detect babies with lysosomal storage disorders and severe early-onset disease in a neonatal screening program. Early diagnosis of these babies is, say the authors, important for timely treatment. The study also demonstrates that there are a large number of mild forms of disease, late-onset cases, and potential asymptomatic cases. The clinical management may be less clear for these categories. The authors conclude: "The findings of our study add relevant information for neonatal screening programmes and draw attention to potential high-risk groups beyond childhood including those with end-stage renal disease, cardiovascular disorders, and cardiomyopathy…better clinical characterisation should help to improve therapy schemes and to justify potentially cost-intensive enzyme replacement therapies."

In a linked Comment, Dr Janice Fletcher, SA Pathology, Women's and Children's Hospital, North Adelaide, and University of Adelaide, Australia, and Dr Bridget Wilcken, Sydney Childrens' Hospitals Network and University of Sydney, Australia, say: "Although there are currently many uncertainties about neonatal screening for lysosomal storage disorders, as suggested by Streubel and colleagues discussion needs to happen, because this is but one example of what is to come; therapeutic and technological possibilities inexorably advance, and the ability to make an early diagnosis by screening efficiently and cheaply will be relevant to many disorders in the foreseeable future."

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Professor Berthold Streubel, Medical University of Vienna, Austria. T) +43-1-40400 2821 E) berthold.streubel@meduniwien.ac.at

Dr Janice Fletcher, SA Pathology, Women's and Children's Hospital, North Adelaide, and University of Adelaide, Australia. T) +61 81618742 E) janice.fletcher@adelaide.edu.au


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