Abstract
Lysosomal storage disorders (LSDs) are a group of genetic disorders characterized by deficiency of specific lysosomal enzymes. In general, patients are clinically normal at birth, and progressively develop severe signs and symptoms. Diagnosis is usually made several years after onset of manifestations, preventing patients to have the benefits of the early treatment. Newborn screening programs are being considered for LSDs to allow early diagnosis and treatment. The present study evaluated the feasibility of a customized screening approach based on modified fluorometric assays with reduced amounts of reagents, substrates and samples for: mucopolysaccharidosis (MPS) type I (MPS I), MPS VI, Fabry, Gaucher, and Pompe diseases. We also evaluated the advantages of including blood chitotriosidase and urinary glycosaminoglycans in the protocol. By the measurement of the specific disease-associated enzymes (plus blood chitotriosidase and urinary glycosaminoglycans) we analyzed 834 de-identified DBS of unselected newborns. No positive case was detected, and the false-positive rates were low. Taking into consideration the limitations of this methodology, we believe that, after defining proper cutoffs, it could be a viable alternative to provide NBS for LSDs by laboratories that may not be able to afford the commercial methods available.
Highlights
Lysosomal storage disorders (LSDs) are a group of inborn errors of metabolism (IEM) that result from the deficiency of specific hydrolases, protein activators or transport proteins, leading to an accumulation of undegraded substrates in lysosomes leading to biochemical changes and even cell death (Tager et al, 1984)
All samples were shipped to the Medical Genetics Service (MGS) of Hospital de Clínicas de Porto Alegre (HCPA) and stored at -20 °C
Newborn screening for lysosomal diseases has been performed regularly since 2006 for Krabbe disease, in the state of New York, USA (Orsini et al, 2016), and is being included in the newborn screening panels by several states in the USA (Hopkins et al, 2015; Burton et al, 2017), being already an official recommendation for MPS I and Pompe (Minter Baerg et al, 2018)
Summary
LSDs include over 50 genetic disorders with specific characteristics (Bellettato and Scarpa, 2010). They are considered individually rare, when combined they are estimated to occur in 1:7,700 live births (Meikle et al., 1999). The incidence of LSDs in Brazil is still not clear. A study reported that LSD corresponded to 60% of the IEM diagnosed from 1982 to 2015 at a reference laboratory in Brazil (Giugliani et al, 2017). Newborn screening (NBS) allows the early diagnosis of several congenital disorders that are mainly asymptomatic at the newborn period. The diagnosis allows early treatment in order to at least slow down the disease progression (http://portalms.saude.gov.br/acoes-e-programas/programanacional-da-triagem-neonatal). The tests included in an NBS program should be based in a reliable methodology and should have the possibility of multiplexing
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