Biochemical diagnosis of aromatic-L-amino acid decarboxylase deficiency (AADCD) by assay of AADC activity in plasma using liquid chromatography/tandem mass spectrometry.

Autor:	Civallero G; BioDiscovery Laboratory and Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.; INAGEMP, Porto Alegre, Brazil., Kubaski F; BioDiscovery Laboratory and Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.; PPGBM and Department of Genetics, UFRGS, Porto Alegre, Brazil., Pereira D; Waters Technologies Brazil, São Paulo, Brazil.; Innovatox, São Paulo, Brazil., Rübensam G; Centro de Pesquisa em Toxicologia e Farmacologia, PUC, Porto Alegre, Brazil., Herbst ZM; Department of Chemistry, University of Washington, Seattle, USA., Silva C; Waters Technologies Brazil, São Paulo, Brazil., Trapp FB; BioDiscovery Laboratory and Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil., Poletto E; BioDiscovery Laboratory and Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.; PPGBM and Department of Genetics, UFRGS, Porto Alegre, Brazil., Faqueti L; BioDiscovery Laboratory and Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil., Iop G; BioDiscovery Laboratory and Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil., Soares J; BioDiscovery Laboratory and Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil., van der Linden V; Centro de Reabilitação Dr Henrique Santillo, Goiania, Brazil., van der Linden H; Centro de Reabilitação Dr Henrique Santillo, Goiania, Brazil., Lourenço CM; Centro Universitario Estacio, Ribeirão Preto, Brazil., Giugliani R; BioDiscovery Laboratory and Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.; INAGEMP, Porto Alegre, Brazil.; PPGCM, UFRGS, Porto Alegre, Brazil.; DASA, São Paulo, Brazil.; House of rares, Porto Alegre, Brazil.
Jazyk:	angličtina
Zdroj:	Molecular genetics and metabolism reports [Mol Genet Metab Rep] 2022 Jun 21; Vol. 32, pp. 100888. Date of Electronic Publication: 2022 Jun 21 (Print Publication: 2022).
DOI:	10.1016/j.ymgmr.2022.100888
Abstrakt:	Aromatic l-amino acid decarboxylase (AADC, EC 4.1.1.28) deficiency is a rare genetic disorder characterized by developmental delay, oculogyric crises, autonomic dysfunction and other problems, caused by biallelic mutations in the DDC gene leading to deficient activity of aromatic l-amino acid decarboxylase, an enzyme involved in the formation of important neurotransmitters, such as dopamine and serotonin. A clinical development program of gene therapy for AADC deficiency is ongoing. An important step for the success of this therapy is the early and precise identification of the affected individuals, but it has been estimated that around 90% of the cases remain undiagnosed. The availability measurement of the AADC activity is mandatory for an accurate biochemical diagnosis. Based on these statements, our objectives were to develop a liquid chromatography tandem mass spectrometry (LC-MS/MS) method suitable for the determination of the AADC activity, and to evaluate its capacity to confirm the deficiency of AADC in potential patients in Brazil. The AADC activities were measured in plasma samples of seven AADC deficient patients and 35 healthy controls, after enzymatic reaction and LC-MS/MS analysis of dopamine, the main reaction product. The results obtained showed clear discrimination between confirmed AADC deficient patients and healthy controls. The method presented here could be incorporated in the IEM laboratories for confirmation of the diagnosis of when a suspicion of AADC deficiency is present due to clinical signs and/or abnormal biomarkers, including when an increased level of 3- O -methyldopa (3-OMD) is found in dried blood spots (DBS) samples from high-risk patients or from newborn screening programs. (© 2022 The Authors.)
Databáze:	MEDLINE
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