RESUMO
INTRODUCTION: Acylcarnitine measurement in blood is a useful test for the diagnosis of inherited errors of mitochondrial fatty acid beta-oxidation. However, there are few data in the literature on the reference ranges of the various acylcarnitines and on whether these reference ranges are age- or sex-dependent. OBJECTIVES: To draw attention to inherited errors of mitochondrial fatty acid beta-oxidation and to establish reference acylcarnitine values in children. PATIENTS AND METHODS: A total of 309 blood samples from healthy children divided into four age groups (group A: <1 month; group B: 1-12 months; group C: 1-7 years; group D: 7-18 years) were obtained and analyzed using tandem mass spectrometry. RESULTS AND CONCLUSION: Reference acylcarnitine values in children are provided. No significant differences were found in relation to age or sex. Our results differ from those reported in the literature reviewed. Importantly, hydroxyacylcarnitines and glutaryl carnitine are absent when normal samples are processed. We review the literature on the main clinical and laboratory findings in mitochondrial fatty acid beta-oxidation deficiencies.
Assuntos
Carnitina/análogos & derivados , Ácidos Graxos/metabolismo , Erros Inatos do Metabolismo Lipídico/sangue , Erros Inatos do Metabolismo Lipídico/diagnóstico , Doenças Mitocondriais/diagnóstico , Adolescente , Carnitina/sangue , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Doenças Mitocondriais/sangue , Oxirredução , Valores de ReferênciaRESUMO
INTRODUCTION: Tandem mass spectrometry (MS/MS) provides a multi-analyte technology for the detection of disorders characterised by the presence of abnormal concentrations of metabolites related to neurological deterioration. It has been recently recommended the use of this technique for early diagnosis of inherited metabolic diseases using cord blood. AIMS: To draw the attention to the inherited metabolic diseases detected by tandem mass spectrometry and to establish reference values for acylcarnitines in cord blood. PATIENTS AND METHODS: One hundred and thirty cord blood specimens from full-term and normal birth weight children (78 males and 52 females) were analysed by MS/MS. RESULTS AND CONCLUSION: Reference values for acylcarnitines from cord blood by MS/MS as a tool for the diagnosis of some neurometabolic diseases are provided. No statistical significant difference between sexes was found. We reviewed the literature related to the diagnosis of inherited metabolic diseases, with emphasis in fatty acid mitochondrial beta-oxidation using MS/MS.
Assuntos
Carnitina/análogos & derivados , Carnitina/sangue , Sangue Fetal/química , Doenças Metabólicas/sangue , Doenças Metabólicas/diagnóstico , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/diagnóstico , Feminino , Humanos , Recém-Nascido , Masculino , Espectrometria de Massas , Doenças Metabólicas/complicações , Doenças do Sistema Nervoso/complicações , Valores de Referência , Fatores de TempoRESUMO
Se han encontrado concentraciones anormales de carnitina en niños asociadas con deficiencias primaria y secundaria de carnitina, con disminución de las concentraciones en sangre y tejidos, así como niveles elevados en algunos errores innatos del metabolismo. El presente estudio tiene como objetivo la obtención de valores de referencia para carnitina libre y total en sangre de cordón umbilical, como herramienta en el diagnóstico temprano de errores innatos del metabolismo. Se analizaron mediante espectrometría de masas en tándem (MS/MS) 130 muestras de sangre de cordón umbilical de nacimientos con embarazos a término y peso normal al nacer (78 niños y 52 niñas) de una población colombiana. No se encontró diferencia estadísticamente significativa dependiendo del sexo del recién nacido. Reportamos valores de referencia para carnitina libre y total en sangre de cordón umbilical de 18,5+/-3,4 micromol/L y 20,9 +/- micromol/L respectivamente.
Assuntos
Humanos , Feminino , Recém-Nascido , Sangue , Carnitina , Cordão Umbilical , ColômbiaRESUMO
Free and total carnitine quantification is important as a complementary test for the diagnosis of unusual metabolic diseases, including fatty acid degradation disorders. The present study reports a new method for the quantification of free and total carnitine in dried plasma specimens by isotope dilution electrospray tandem mass spectrometry with sample derivatization. Carnitine is determined by looking for the precursor of ions of m/z = 103 of N-butylester derivative, and the method is validated by comparison with radioenzymatic assay. We obtained an inter- and intra-day assay coefficient of variation of 4.3 and 2.3, respectively. Free and total carnitine was analyzed in 309 dried plasma spot samples from children ranging in age from newborn to 14 years using the new method, which was found to be suitable for calculating reference age-related values for free and total carnitine (less than one month: 19.3 +/- 2.4 and 23.5 +/- 2.9; one to twelve months: 28.8 +/- 10.2 and 35.9 +/- 11.4; one to seven years: 30.7 +/- 10.3 and 38.1 +/- 11.9; seven to 14 years: 33.7 +/- 11.6, and 43.1 +/- 13.8 micro M, respectively). No difference was found between males and females. A significant difference was observed between neonates and the other age groups. We compare our data with reference values in the literature, most of them obtained by radioenzymatic assay. However, this method is laborious and time consuming. The electrospray tandem mass spectrometry method presented here is a reliable, rapid and automated procedure for carnitine quantitation.
Assuntos
Carnitina/sangue , Doenças Metabólicas/sangue , Espectrometria de Massas por Ionização por Electrospray/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Doenças Metabólicas/diagnóstico , Radioimunoensaio , Valores de ReferênciaRESUMO
Free and total carnitine quantification is important as a complementary test for the diagnosis of unusual metabolic diseases, including fatty acid degradation disorders. The present study reports a new method for the quantification of free and total carnitine in dried plasma specimens by isotope dilution electrospray tandem mass spectrometry with sample derivatization. Carnitine is determined by looking for the precursor of ions of m/z = 103 of N-butylester derivative, and the method is validated by comparison with radioenzymatic assay. We obtained an inter- and intra-day assay coefficient of variation of 4.3 and 2.3, respectively. Free and total carnitine was analyzed in 309 dried plasma spot samples from children ranging in age from newborn to 14 years using the new method, which was found to be suitable for calculating reference age-related values for free and total carnitine (less than one month: 19.3 ± 2.4 and 23.5 ± 2.9; one to twelve months: 28.8 ± 10.2 and 35.9 ± 11.4; one to seven years: 30.7 ± 10.3 and 38.1 ± 11.9; seven to 14 years: 33.7 ± 11.6, and 43.1 ± 13.8 æM, respectively). No difference was found between males and females. A significant difference was observed between neonates and the other age groups. We compare our data with reference values in the literature, most of them obtained by radioenzymatic assay. However, this method is laborious and time consuming. The electrospray tandem mass spectrometry method presented here is a reliable, rapid and automated procedure for carnitine quantitation
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Carnitina , Doenças Metabólicas , Espectrometria de Massas por Ionização por Electrospray , Doenças Metabólicas , Radioimunoensaio , Valores de ReferênciaRESUMO
INTRODUCTION: The metabolic screening test gives the first laboratory indication for neurometabolic alterations which can cause mental retardation. Some techniques such as thin layer chromatography, are still used in several countries to confirm the diagnosis of inborn errors of metabolism after a general screening test. PATIENTS AND METHODS: Two patients from a mentally retarded Colombian population were reported positive for the Nitrosonaphtol test, and remained positive to tyrosine metabolism alteration by thin layer chromatography, suggesting the correspondent management. In the present study we tried to confirm the last diagnosis, performing tandem mass spectrometry analysis of acylcarnitines and amino acids, on blood samples of all patients from the last study, which were found negative for any alteration. CONCLUSION: Is necessary to improve the diagnosis methods used in some countries in order to avoid mistakes that can change the life-style of the wrongly diagnosed patients.
Assuntos
Encéfalo/metabolismo , Erros de Diagnóstico , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/etiologia , Tirosinemias/complicações , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Espectrometria de Massas/métodos , Fenilcetonúrias/diagnóstico , Tirosina/metabolismo , Tirosinemias/diagnósticoRESUMO
Carnitine-acylcarnitine translocase deficiency is a newly recognized inborn error of metabolism that involves transport of long-chain fatty acids into mitochondria, which in turn impairs mitochondrial beta-oxidation, and ketogenesis. We report a new familial example; the affected twins had neonatal distress, hyperammonemia, and transient intracardiac conduction defects. Clinical and biochemical analysis of both our patients and the two previously reported patients revealed that this inherited defect could be manifested during the neonatal period without any of the signs classically associated with fatty oxidation defects. In contrast, all four patients had sustained and "isolated" hyperammonemia, which could be misinterpreted as being caused by urea cycle defects. We conclude that carnitine-acylcarnitine translocase deficiency is a potential differential diagnosis in neonates with unexplained neonatal hyperammonemia. Cardiac and muscle involvement may represent further early pivotal symptoms.