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KFSH & RC
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Newborn
Screening
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Although early diagnosis for some of the metabolic disorders has proven to be effective in treatment or management, neonates are screened for only a handful of diseases, even in the developed world. The fact that many of the disorders are "silent," whereby irreversible neurological damage occurs without any signs to alert the family, is ample justification for Newborn Screening (NBS).
For more than thirty years, Dr. Guthrie's bacterial inhibition test for phenylalanine in dried blood spots from two to five day old infants has formed the basis for successful national NBS programs for Phenylketonuria (PKU) in the developed world. Similar methods were adopted on a limited scale for other diseases such as galactosemia, maple syrup urine disease, and others. However, methods either for NBS or specialized biochemical tests for sick infants, share some, if not all, of the following drawbacks: narrow spectrum of diseases covered by each method, high false-positive rates, laborious sample preparations, and long analytical time.
Tandem Mass Spectrometry (MSMS) & Inborn Errors of Metabolism
The employment of tandem mass spectrometry (MSMS) technology for the diagnosis of inborn errors of metabolism, particularly organic acidemias and amino acid disorders, was introduced in the early 1990's by Millington and colleagues at Duke University. The concept was to use this sensitive, specific, and powerfull analytical technique to overcome some of the drawbacks of the classic methods described above. The use of MSMS in the analysis of dried blood spots eliminates the need for chromatography (which reduces analysis time to two minutes per sample), broaden the spectrum of diseases covered by a single test (to >20 diseases), and reduces the false-positive rates.
Our laboratory is one of only a handful of laboratories worldwide that applies the MSMS technology as a diagnostic tool for metabolic disorders. This laboratory is a leader in its field due to the following reasons: We were the first in the field to achieve automation of MSMS analysis of samples, which allowed the unattended analysis of five hundred blood spots per instrument per day. This method was established as a powerful diagnostic tool for over twenty five diseases, and its value in quantifying many important metabolites was established. The laboratory was the first to develop a simple microplate-based batch process, which reduces the time of a sample preparation to approximately two hours per ninety six samples. And finally, the section was the first to introduce and validate a Computer Assisted Metabolic Profiling Algorithm (CAMPA) for automatic calculation of metabolite concentrations and flagging of abnormal results.