Neonatal screening for four lysosomal storage diseases with a digital microfluidics platform: Initial results in Brazil.

We describe the initial results of a neonatal screening program for four lysosomal storage diseases (MPS I, Pompe, Gaucher and Fabry) using the digital microfluidics methodology. The method successfully identified patients previously diagnosed with these diseases and was used to test dried blood spot samples obtained from 10,527 newborns aged 2 to 14 days. The digital microfluidic technology shows potential for a simple, rapid and high-throughput screening for these four diseases in a standard neonatal screening laboratory.

Investigation of newborns with abnormal results in a newborn screening program for four lysosomal storage diseases in Brazil.

Lysosomal storage diseases (LSDs) are genetic disorders, clinically heterogeneous, mainly caused by defects in genes encoding lysosomal enzymes that degrade macromolecules. Several LSDs already have specific therapies that may improve clinical outcomes, especially if introduced early in life. With this aim, screening methods have been established and newborn screening (NBS) for some LSDs has been developed. Such programs should include additional procedures for the confirmation (or not) of the cases that had an abnormal result in the initial screening. We present here the methods and results of the additional investigation performed in four babies with positive initial screening results in a program of NBS for LSDs performed by a private laboratory in over 10,000 newborns in Brazil. The suspicion in these cases was of Mucopolysaccharidosis I - MPS I (in two babies), Pompe disease and Gaucher disease (one baby each). One case of pseudodeficiency for MPS I, 1 carrier for MPS I, 1 case of pseudodeficiency for Pompe disease and 1 carrier for Gaucher disease were identified. This report illustrates the challenges that may be encountered by NBS programs for LSDs, and the need of a comprehensive protocol for the rapid and precise investigation of the babies who have an abnormal screening result.

Tirosemia neonatal transitória: uma alteraçäo freqüente / Transient neonatal tyrosinemia: a frequent abnormality

Objetivos: Avaliar a freqüência da tirosinemia neonatal transitória, com ou sem hiperfenilalaninemia secundária, observada através da triagem neonatal para erros inatos do metabolismo ("teste do pezinho"), e a necessidade de monitoramento e eventual intervençäo medicamentosa o/ou dietética em casos específicos. Métodos: Foram analisadas 457.870 amostras de sangue seco obtido por punçäo de calcâneo de crianças de 3 a 20 dias de vida, através de cromatografia qualitativa de aminoácidos em camada delgada. Os casos positivos foram confirmados quantitativamente em amostras séricas pelas dosagens fluorimétricas da tirosina e da fenilalanina. Resultados: 1.231 amostras de sangue seco impregnado em papel filtro apresentaram resultados positivos para tirosina na avaliaçäo cromatográfica. A análise sérica por método fluorimétrico revelou valores normais de tirosina e fenilalanina em 822 pacientes; os restantes 409 apresentaram tirosina elevada e foram divididos em três grupos de acordo com a concentraçäo de tirosina observada. Em 118 destes pacientes foram observados também níveis de fenilalanina superiores ao limite de referência. Conclusöes: A tirosinemia neonatal transitória é um distúrbio muito freqüente em recém-nascidos (1/372), sendo que em alguns casos também säo registrados elevados níveis de fenilalanina. Enquanto näo estiver demonstrado que esse achado é completamente inócuo, o monitoramento desses pacientes e o eventual emprego de medidas que reduzem os níveis de tirosina e fenilalanina devem ser considerados pelo pediatra.