Findings of an article published Online First in The Lancet show that an analysis of dried blood spots from around 35,000 babies in Austria has demonstrated that lysosomal storage disorders are more common than previously thought, even though they remain rare. The finding raises questions in terms of potential screening practicality and its related cost.
Lysomol storage disorders are a group of rare inherited metabolic disorders that result from defects in lysosomal function when a specific organelle in the body’s cells, the lysosome, malfunctions.
According to estimations made prior to this study, the overall incidence of such disorders, including Pompe’s disease, Fabry’s disease and Gaucher’s disease, affects 1 per 7,700 births in white people. With the introduction of electrospray ionization tandem mass spectrometry (ESI-MS), in which amino acids and acylcarnitines, another metabolite, were measured simultaneously, researchers were able to identify several of these disorders for the first time in 1993.
Together with advanced technological capacities, neonatal screenings programs are currently able to identify a broad range of disorders, which result in clinical benefits due to early detection and presymptomatic treatment.
Further interest in this field has been raised by the recent development of enzyme replacement therapies.
Another yet more controversial benefit of such expanded programs is that parents now have the opportunity to receive information regarding the risk of having children with similar disorders.
Cells throughout the body can develop a progressive lysosomal substrate deposition, resulting in a gradual deterioration of renal function to end-stage renal disease, cardiovascular, cerebrovascular or neurological disease, cardiomyopathy, muscle weakness as well as other conditions.
Professor Berthold Streubel at the Medical University of Vienna in Austria and his team consecutively collected dried blood spots specimens from 34,736 newborns between January and July 2010 as part of the national routine Austrian newborn screening program.
They analyzed all 34,736 anonymized samples for enzyme activity that indicated a lysosomal storage disorder and detected low enzyme activities in 38 babies.
After analyzing all samples for mutations they discovered 15 cases of lysosomal storage disorders, with the most frequent mutations being Fabry’s disease with 1 per 3,859 births, followed by Pompe’s disease with 1 per 8,684 births, and Gaucher’s disease with 1 per 17,368 births, resulting in a higher than expected combined incidence of 1 per 2,315 births. According to the researchers, the mutation spectrum indicated a high number of late-onset diseases.
In the near future, three US states have passed legislation to include several lysosomal storage disorders in their neonatal screening programs, with Washington State conducting a pilot study to detect mucopolysaccharidosis type I, Pompe’s – and Fabry’s disease. In 2011, the regional neonatal screening program will start in Florence, Italy.
According to the authors, neonatal screening programs are usually intended to identify babies with disorders to enable early detection and urgent presymptomatic treatment to avoid serious clinical harm. They say that their study demonstrates the technical feasibility of identifying babies with lysosomal storage disorders, and severe early-onset disease in neonatal screening programs, and point out that early diagnosis is important for timely treatment. The study also shows a large number of mild forms of disease, potential asymptomatic cases and late-onset cases for which clinical management may be less clear.
The authors say in a concluding statement:
“The findings of our study add relevant information for neonatal screening programs and draw attention to potential high-risk groups beyond childhood including those with end-stage renal disease, cardiovascular disorders, and cardiomyopathy…better clinical characterization should help to improve therapy schemes and to justify potentially cost-intensive enzyme replacement therapies.”
Dr Janice Fletcher, SA Pathology at the Women’s and Children’s Hospital in North Adelaide and the University of Adelaide, Australia, and Dr Bridget Wilcken of Sydney Childrens’ Hospitals Network and University of Sydney in Australia, say in a linked comment:
“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.”
Written by Petra Rattue