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1.
Chinese Medical Journal ; (24): 216-219, 2008.
Artigo em Inglês | WPRIM | ID: wpr-255733

RESUMO

<p><b>BACKGROUND</b>Methylmalonic aciduria (MMA) is the most frequent disease of organic aciduria in China. Various biochemical strategies are followed for the prenatal diagnosis of MMA. However, since fetuses affected by MMA have decreased excretion of methylmalonic acid, the difficulties of prenatal biochemical diagnosis are obvious. Gas chromatography mass spectrometry (GC/MS) and tandem mass spectrometry (ESI/MS/MS) have allowed us to identify the disease in affected fetuses. The aim of this study was to determine the value of analysis of organic acids and total homocysteine in amniotic fluid in prenatal diagnosis of MMA.</p><p><b>METHODS</b>The clinical diagnoses and outcomes of nine probands with MMA and the prenatal diagnoses based on biochemical analysis of nine fetuses at risk for MMA were investigated. Amniotic fluid samples from pregnancies at risk for MMA and metabolically normal pregnancies were obtained at 16 - 24 weeks of gestation. Methylmalonic acid and methylcitric acid were measured by GC/MS, propionylcarnitine was analyzed by ESI/MS/MS, and total homocysteine was determined by fluorescence polarization immunoassay.</p><p><b>RESULTS</b>In two pregnancies, high levels of methylmalonic acid, methylcitric acid, propionylcarnitine, and total homocysteine indicated combined MMA and homocysteinemia in the fetuses. One of the mothers continued pregnancy and received cobalamin supplement as prenatal treatment, and the other terminated her pregnancy. In one pregnancy, significantly elevated levels of methylmalonic acid, methylcitric acid, and propionylcarnitine, and normal level of total homocysteine was found indicating isolated MMA in the fetus; abortion was performed on this case. In the other six pregnancies, all the levels of the above mentioned metabolites were normal suggesting that the fetuses were not affected by MMA. The diagnoses were confirmed after delivery by testing urinary organic acids and plasma total homocysteine.</p><p><b>CONCLUSIONS</b>The metabolic abnormalities of MMA occur early in gestation. The level of total homocysteine in amniotic fluid may be an additional indicator of fetal combined MMA and homocysteinemia. Determination of total homocysteine level in amniotic fluid may become a convenient and reliable method for prenatal diagnosis of the disease.</p>


Assuntos
Feminino , Humanos , Masculino , Gravidez , Líquido Amniótico , Química , Carnitina , Citratos , Cromatografia Gasosa-Espectrometria de Massas , Homocisteína , Sangue , Ácido Metilmalônico , Urina , Diagnóstico Pré-Natal , Métodos , Espectrometria de Massas por Ionização por Electrospray
2.
Annals of the Academy of Medicine, Singapore ; : 120-123, 2008.
Artigo em Inglês | WPRIM | ID: wpr-244441

RESUMO

From June 1998 to May 2007, 9566 urine samples were collected from patients with psychomotor deficits, seizures, vomiting and unconsciousness in Peking University First Hospital. Their urine organic acids profiles were analysed using gas chromatography - mass spectrometry (GCMS), GCMS solution and Inborn Errors of Metabolism Screening System software. In all patients, blood acylcarnitines were analysed using tandem mass spectrometry. One hundred and sixty-eight patients (1.76%) with organic acidurias were detected. Among them, 116 (116/ 168, 69.0%) had methylmalonic aciduria, 63 (54.3%) of these 116 patients had methylmalonic aciduria combined with homocysteinemia. Sixteen (9.5%) of those patients detected with organic acidurias had propionic aciduria, and 15 (8.9%) had multiple carboxylase deficiency. Seven (4.2%) had glutaric aciduria type 1. After dietary treatment, medicine and rehabilitation, clinical improvements were observed in more than half of the patients. Twenty-eight of the 168 patients (16.7%) recovered and led a normal life. The method of urine organic acid analysis by gas chromatography - mass spectrometry and blood acylcarnitines analysis by tandem mass spectrometry have been established and applied successfully in China, namely Beijing, Shanghai, Wuhan and Guangzhou. The prognoses of Chinese patients with organic acidurias have also improved significantly.


Assuntos
Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , China , Doenças Metabólicas , Urina , Ácido Metilmalônico , Urina , Deficiência Múltipla de Acil Coenzima A Desidrogenase , Urina , Acidemia Propiônica , Urina
3.
Annals of the Academy of Medicine, Singapore ; : 13-15, 2008.
Artigo em Inglês | WPRIM | ID: wpr-244439

RESUMO

Nationwide neonatal mass screening for inherited metabolic diseases has started in Japan since 1977. At least 8000 children have probably been spared from handicaps resulting from such diseases over the past 30 years. Recently remarkable changes have been made to the evolving neonatal screening system. Declining birth rate and economic problems in Japan have demanded a more effective neonatal screening system. Development of new innovative screening methods and treatment tools, e.g. tandem mass spectrometry (MS/MS) technology and enzyme replacement therapy for mucopolysaccharidosis (MPS), have facilitated expansion of target diseases in neonatal screening. We have carried out pilot screening using MS/MS in 6 laboratories in Japan. The incidence of inherited metabolic diseases was found to be 1 in 9330 (65 cases out of 606,380 babies screened) during the period between 1997 and 2007. The incidence was lower than those of Europe or USA (about 1 in 4000 to 5000). The disease frequency between unscreened symptomatic cases and asymptomatic cases detected through MS/MS screening were also found to be different. In MS/MS screening, the most common organic acidemia was propionic acidemia, whereas in symptomatic cases, methylmalonic acidemia was the most common. Further study of ethnic diversity in severity of propionic academia is required. The outcomes of patients detected in the MS/MS screening were significantly favourable. The results showed the benefits of MS/ MS screening. The diagnostic support network for gas chromatography-mass spectrometry (GC/ MS) analysis and enzyme determination has also been developed. We have developed an automated system of GC/MS data processing and auto-diagnosis which allowed the GC/MS data processing to be extremely fast and simple. Enzyme evaluation for diagnostic support for screening, including a method using peripheral blood and high performance liquid chromatography (HPLC), and another method of in-vitro probe assay using cultured cells and MS/MS. Furthermore, re-location of screening laboratories for a more efficient screening network will be required such that at least 30,000 samples can be analysed in each laboratory.


Assuntos
Humanos , Recém-Nascido , Japão , Erros Inatos do Metabolismo , Diagnóstico , Triagem Neonatal , Métodos , Padrões de Referência , Espectrometria de Massas em Tandem
4.
Chinese Journal of Pediatrics ; (12): 249-251, 2003.
Artigo em Chinês | WPRIM | ID: wpr-345465

RESUMO

<p><b>OBJECTIVE</b>To investigate the clinical and neurodevelopmental profiles of patients with biotinidase deficiency and to determine the efficacy of current therapy with respect to outcome.</p><p><b>METHODS</b>Six patients aged from 3 months to 14 years with biotinidase deficiency were confirmed by urinary organic acid analysis with gas chromatography/mass spectrometry (GC/MS) and biotinidase assay on dried blood spots. Biotin was supplemented individually (10-40 mg/d). Their clinical features, laboratory findings, and treatment regimen were reviewed.</p><p><b>RESULTS</b>All the 6 patients presented with some extent of neurological abnormalities and dermatological lesions. Cases 1 - 3 had poor feeding, vomiting, seizures, mental retardation, and lethargy onset from their early infancy, with varied degree of anemia, ketosis, acidosis, and hypoglycemia. Case 2 exhibited eczema and dermatitis from his age of 7 months. Case 4 displayed motor deficit and ataxia after 6 months of age, and generalized pustular psoriasis when he was 8 months old. Cases 5 and 6 gradually showed muscle weakness and paraplegia at the age of 7 years and 5 years, respectively. Inflammatory demyelination changes of cervical cord were evident on magnetic resonance imaging in these two patients. Case 6 had progressive optic atrophy, eczema and alopecia. Remarkable elevations of urinary lactate, pyruvate, 3-OH-propionate, methylcitrate, propionylglycine, 3-OH-isovalerate, 3-methylcrontonylglycine were confirmed in cases 1, 2, 3 and 5. Slight increase of urinary lactate, pyruvate, and 3-methylcrontonylglycine was observed in cases 4 and 6. Biotinidase activities assayed on dried blood spots from all the patients were below 0.1 pmol/(min.3 mm) Biotin supplementation for all the patients, except for case 3 who was not treated, resulted in pronounced and rapid clinical and biochemical improvement. Cases 4 and 6 had residual neurological damage comprising ataxia and motor handicap of legs, due to prolonged disease course.</p><p><b>CONCLUSIONS</b>Biotinidase deficiency intensively impairs nervous system and skin in the affected patients. Urinary organic acid analysis and blood biotinidase assay are crucial to the diagnosis. Early diagnosis and biotin supplementation can contribute significantly to the improvement of prognosis.</p>


Assuntos
Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Masculino , Biotina , Usos Terapêuticos , Deficiência de Biotinidase , Diagnóstico , Tratamento Farmacológico , Urina , Cromatografia Gasosa-Espectrometria de Massas , Resultado do Tratamento
5.
Journal of the Korean Pediatric Society ; : 866-872, 1996.
Artigo em Coreano | WPRIM | ID: wpr-32553

RESUMO

Tyrosinemia type 1 is an autosomal recessive disorder caused by deficiency of the enzyme fumarylacetoacetate hydrolase(FAH). The disease is characterized by hepatic dysfuntion, hepatocellular carcinomas, renal tubular dysfunction, rickets, and neurologic crises. Two forms of the disease, acute and chronic, are thought to be from the residual enzyme activity in the liver. The diagnosis of the tyrosinemia type 1 is suggested by elevated plasma tyrosine, supported by increased urinary succinylacetone, and confirmed by reduced FAH activity in cultured fibroblasts. We had a 5 month old Korean boy with acute tyrosinemia type 1 who presented with recurrent sepsis-like episodes since 2 months of age, progressive liver dysfunction, and rickets. Plasma amino acid analysis showed markedly elevated tyrosine, methionine and urine amino acid analysis was suggestive of Fanconi syndrome showing generalized aminoaciduria. Organic acid analysis by Gas Chromatography/Mass Spectrometry detected large amount of succinylacetone excreted in the urine. Delta-aminolevulinic acid was elevated as well. X-ray findings were characteristics of rickets and abdominal sonogram, CT and MRI revealed cirrhotic liver with varying size of multiple nodules. Liver transplantation was strongly recommended throughout his clinical course but refused by parents, and he died of hepatic failure at the age of 8 months. Autospy was perfomed showing macro and micronodular liver cirrhosis. Kidney was markedly enlarged, however, glomeruli and tubules were relatively unaltered. Mutation analysis is under the study.


Assuntos
Humanos , Lactente , Masculino , Doença Aguda , Ácido Aminolevulínico , Carcinoma Hepatocelular , Diagnóstico , Síndrome de Fanconi , Fibroblastos , Rim , Fígado , Cirrose Hepática , Hepatopatias , Falência Hepática , Transplante de Fígado , Imageamento por Ressonância Magnética , Metionina , Pais , Plasma , Raquitismo , Análise Espectral , Tirosina , Tirosinemias
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