Study of 3-0-Methyldopa quantification for possible integration into the portuguese newborn screening program

Santos, Raquel Alexandra Martins

http://hdl.handle.net/10400.22/29804

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Authors

Santos, Raquel Alexandra Martins

Advisor(s)

Rocha, Hugo Daniel Azevedo

Silva, Regina Augusta Alves Pereira da

Abstract(s)

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder that impairs neurotransmitter synthesis, leading to severe neurological and developmental symptoms. Early diagnosis through newborn screening is essential for timely and appropriate treatment. The quantification of 3-0-methyldopa (3-OMD), a metabolite that accumulates in AADC deficiency, in dried blood spot (DBS) samples is a viable and minimally invasive method for detecting this condition. This study assessed the feasibility of integrating 3-OMD quantification into the current protocol used in the Portuguese Newborn Screening Program using flow injection anlysis coupled with tandem mass spectometry (FIA-MS/MS). After the method was implemented and optimized, it was validated in terms of sensivity, specificity, and precision, without interfering with the detection of other biomarkers. For samples with elevated 3-OMD levels, a second-tier test using liquid chromatography-tandem mass spectometry (LC-MS/MS) was developed to resolve potential interferences. Although no cases of AADC deficiency were identified in this cohort, the method consistently quantified 3-OMD, detecting elevated levels in patients undergoing levodopa therapy. These results demonstrate that integrating 3-OMD quantification into the existing newborn screening workflow is feasible, presenting a promising approach for the early detection of AADC deficiency.