Simplified method for the chemical diagnosis of organic aciduria using GC/MS

Nakagawa, Katsuhiro; Kawana, Shuichi; Hasegawa, Yuki; Yamaguchi, Seiji

doi:10.1016/j.jchromb.2010.02.020

Cited by 18 publications

(8 citation statements)

References 23 publications

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“…The combination of MS/MS to detect the serum amino and fatty acid profiles, and GC/MS to detect urinary organic acid is widely used in clinical practice. It has provided exact diagnostic criteria for IDM diagnosis as well as a theoretical basis for its treatment ( 15 – 17 ). In the present study, we applied GC/MS to detect the urinary metabolic components of 56 IE children, and 25 cases were confirmed with 12 types of abnormalities, of which there were 5 cases of methylmalonic aciduria, 5 cases of ketotic dicarboxylic aciduria, 3 cases of phenylketonuria, and 3 cases of non-ketotic dicarboxylic aciduria.…”

Section: Discussionmentioning

confidence: 99%

Screening of inherited metabolic abnormalities in 56 children with intractable epilepsy

Liu

Chen

et al. 2016

Experimental and Therapeutic Medicine

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Epilepsy is a common children's neural disease that is largely controlled by anti-epileptic drugs. Nevertheless, children experience repeated attacks that develop into intractable epilepsy (IE). The aim of the present study was to examine the inherited metabolic abnormalities in children with IE to provide early etiological and symptomatic treatment. Urine and blood samples of 56 children with IE served as the experimental group and 56 cases of children with IE, who were successfully treated served as the control group, and analyzed by gas chromatography-mass spectrometry and tandem mass spectrometry for the metabolic screening of amino, organic, and fatty acids. Urine routine, hepatic function, blood biochemistry, imageology of encephalon and brain stem-evoked potential (auditory and optical) were also examined. Of the 27 IE children confirmed as abnormal in urine and blood screening, there were 19 cases (70.3%) of hypoevolutism or retrogression of intelligence and motor function, 15 cases (55.5%) of brain stem-evoked potential and of encephalic computed tomography (CT) or magnetic resonance imaging (MRI) abnormality, 6 cases (22.2%) of abnormal family history and of abnormal blood biochemistry and blood gas analysis, and 5 cases (18.5%) with skin change and of abnormal hepatic function. Of the 27 cases, 11 cases (19.6%) were diagnosed with inherited metabolic diseases. Among the children in the control group, 3 cases showed abnormal urine test results, one of which had family history, one had hypoevolutism or retrogression of intelligence and motor function, one had brain stem-evoked potential and encephalic CT or MRI abnormality, while two of the 3 cases had inherited metabolic abnormalities. The correlation analysis revealed that abnormal urine test was significantly correlated with inherited metabolic abnormalities (P<0.05). Of the 56 IE patients, 25 cases (44.6%) were identified as abnormal under urine screening, and of the 25 cases, 6 cases had simple generalized seizure (24.0%), 5 cases had simple partial seizure (20.0%), 2 cases had multiple types of seizure (8.0%), and 12 cases had infantile spasms (48.0%). Six cases in the control group showed an abnormal urine test, with 3 cases of simple generalized seizure, 2 cases of simple partial seizure and 1 case of multiple types of seizure. The abnormal urine in infantile spasms was often the risk factor of IE. A total of 46 IE children underwent blood screening and 13 cases were diagnosed as abnormal. In conclusion, inherited metabolic abnormality was a common influential factor in the pathogenesis of IE, especially in infantile spasms. Screening of inborn metabolic abnormality in children with IE should be conducted as early as possible, to achieve early treatment and improve their prognosis.

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Section: Discussionmentioning

confidence: 99%

Screening of inherited metabolic abnormalities in 56 children with intractable epilepsy

Liu

Chen

et al. 2016

Experimental and Therapeutic Medicine

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“…Organic acid analysis in the urine by gas chromatography/ mass spectrometry [10] and an MCM activity assay [11] are useful for the diagnosis of this disease. Furthermore, a detailed assay of enzyme activity would be useful not only for the diagnosis but also to assess the degree of severity of the disease; however, no method for measuring subtle differences in activity has yet been reported.…”

Section: Introductionmentioning

confidence: 99%

Assay for methylmalonyl coenzyme A mutase activity based on determination of succinyl coenzyme A by ultrahigh-performance liquid chromatography tandem mass spectrometry

et al. 2015

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Methylmalonic acidemia (MMA) is an inherited metabolic disease. In this condition, metabolism from methylmalonyl coenzyme A (CoA) to succinyl-CoA is inhibited because of either low methylmalonyl-CoA mutase (MCM) activity or adenosylcobalamin deficiency owing to altered vitamin B12 metabolism. A high-precision assay for detecting MCM activity would facilitate not only MMA diagnosis but also the ability to determine the severity of MMA. We developed an MCM assay method based on ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) that involves the determination of succinyl-CoA, which is formed in an enzyme reaction, using peripheral lymphocytes. Using 0.05, 0.5, and 5 μmol/L succinyl-CoA, the intra-assay coefficient of variation (CV) was less than 5.2% and the inter-assay CV was less than 8.7%. The MCM activities of five healthy individuals and four patients were investigated with this assay. The MCM activities of the patients were very low in relation to those of healthy individuals. Together, these results show that the UPLC-MS/MS method is useful for a detailed MCM activity assay.

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“…With the application of GC-MS, MS-MS, enzymological investigation and mutation analysis in the screening and diagnosis of inherited metabolic diseases, more and more organic aciduria patients were found out, especially the MMA [21,22] . In this study, clinical characteristics and gene mutations of Chinese MMA patients were mainly investigated.…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics and gene mutation analysis of methylmalonic aciduria

Qin

Tian

et al. 2011

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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Methylmalonic aciduria (MMA) is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase (MCM, mut complementation group) or in the synthesis of the MCM cofactor adenosylcobalamin (cbl complementation groups). The defects in the mut complementation group accounts for the largest number of patients with isolated MMA. At least 200 mutations in the MUT gene on chromosome 6p12 have been identified in MMA patients until now. This study aimed to investigate the clinical characteristics of MMA and genomic variations in the MUT gene of Chinese patients. Genomic DNA was extracted from 18 patients who were diagnosed as having isolated MMA by gas chromatography/mass spectrometry (GC-MS), and from some of their parents as well. Amplification and direct sequencing of the MUT coding regions (exon 2-13) and their adjacent intronic consensus splice sites were performed in order to identify the disease causing mutations. In this group, six novel mutations in the MUT gene, c.424A>G (p.T142A), c.786T>G (p.S262R), c.808G>C (p.G270R), c.1323_1324insA, c.1445-1G>A and c.1676+77A>C were identified. p.T142A and p.G270R were respectively detected at a heterozygous level in one patient. Two previously reported mutations, c.682C>T (p.R228X) and c.323G>A (p.R108H) were also found in this study. In addition, six previously described single nucleotide polymorphism (SNP), c.636A>G (p.K212K), c.1495G>A (p.A499T), c.1595A>G (p.H532R), c.1992G>A (p.A664A), c.2011G>A (p.V671I) and c.1677-53A>G were identified. In this study, we updated the spectrum of MUT mutations and identified the main MMA-causing mutations in Chinese MMA patients.

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Simplified method for the chemical diagnosis of organic aciduria using GC/MS

Cited by 18 publications

References 23 publications

Screening of inherited metabolic abnormalities in 56 children with intractable epilepsy

Screening of inherited metabolic abnormalities in 56 children with intractable epilepsy

Assay for methylmalonyl coenzyme A mutase activity based on determination of succinyl coenzyme A by ultrahigh-performance liquid chromatography tandem mass spectrometry

Clinical characteristics and gene mutation analysis of methylmalonic aciduria

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