Quantification of methylcitrate in dried urine spots by liquid chromatography tandem mass spectrometry for the diagnosis of propionic and methylmalonic acidemias.
Clin Chim Acta
; 487: 41-45, 2018 Dec.
Article
em En
| MEDLINE
| ID: mdl-30217751
ABSTRACT
Accumulation of methylcitrate is a biochemical hallmark of inborn errors of propionate metabolism, a group of disorders that include propionic acidemia, methylmalonic aciduria and cobalamin defects. In clinical laboratories, this analyte is measured without quantification by gas chromatography mass spectrometry as part of urine organic acids. Here we describe a simple, sensitive and specific method to quantify methylcitrate in dried urine spots by liquid chromatography tandem mass spectrometry. Methylcitrate is extracted and derivatized with 4-[2-(N,N-dimethylamino)ethylaminosulfonyl]-7-(2-aminoethylamino)-2,1,3-benzoxadiazole in a single step. A derivatization mixture was added to 3.2â¯mm disc of dried urine spots, incubated at 65⯰C for 45â¯min and 4⯵l of the reaction mixture were analyzed. Separation was achieved on C18 column with methylcitrate eluting at 3.8â¯min. Intraday and interday imprecision (nâ¯=â¯17) were ≤20.9%. The method was applied on dried urine spots from established patients and controls. In controls (nâ¯=â¯135), methylcitrate reference interval of 0.4-3.4â¯mmol/mol creatinine. In patients, methylcitrate ranged between 8.3 and 591â¯mmol/mol creatinine. Quantification of methylcitrate provides important diagnostic clues for propionic acidemia, methylmalonic aciduria and cobalamin disorders. The potential utilization of methylcitrate as monitoring biomarker of patients under treatment and whether it correlates with the clinical status has yet to be established.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Urinálise
/
Citratos
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Acidemia Propiônica
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Erros Inatos do Metabolismo dos Aminoácidos
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article