Quantification of methylmalonic acid in serum measured by capillary gas chromatography—mass spectrometry as tert.-butyldimethylsilyl derivatives

Straczek, J.; Felden, F.; Dousset, B; Guéant, Jean Louis; Belleville, F.

doi:10.1016/0378-4347(93)80044-5

Cited by 18 publications

(9 citation statements)

References 22 publications

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“…Methionine and methionine/phenylalanine ratio was calculated in the dried blood spots by ABSciex 4500 triple quadrupole tandem mass spectrometer (LC-MS/MS) using Chromsystems kits, respectively (Chromsystems, Germany). Methylmalonic acid (MMA) levels in the urine were measured to rule out cases with combined homocystinuria and methylmalonic aciduria by gas chromatograph-mass spectrometer (GC-MS) using the stable isotope-labeled dilution method described by Straczek et al 18 with slight modifications.…”

Section: Methodsmentioning

confidence: 99%

Seven novel genetic variants in a North Indian cohort with classical homocystinuria

Kaur

Attri

Saini

et al. 2020

Sci Rep

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Classical homocystinuria is the most common cause of isolated homocystinuria. The variants of the CBS gene remain unidentified in Indian children with this disorder. Based on the hallmark clinical features, family history, and/or biochemical clues for classical homocystinuria, 16 children below the age of 18 years were evaluated by Sanger sequencing of the coding exons of CBS gene with flanking intronic regions. The common C677T variant of the MTHFR gene was also screened by restriction fragment length polymorphism. Fifteen children were clinically suspected of having classical homocystinuria and one asymptomatic child with positive family history. Only seven children had biochemical features of classical homocystinuria. Sanger sequencing of the CBS gene confirmed 15 different pathogenic or likely pathogenic variants in 14 cases. Of these, seven variants were novel (three frameshift deletions, two nonsense, one missense, one splice site variant) and were predicted to be deleterious by Mutation Taster software. Seven cases were homozygous, another six were compound heterozygous, and one case was single heterozygous in the study. None of the three most frequent mutations reported worldwide viz., I278T, G307S, and IVS 11-2A>C were found in our cohort. No variants were detected in the exons 2, 8, 12, and 14 as compared to reported literature. Eleven out of 15 variants were associated with the conserved catalytic domain of the CBS polypeptide. The MTHFR polymorphism C677T was observed in heterozygous state in six cases. Our study reports the detailed genotype and seven novel variants in the CBS gene, causing classical homocystinuria in Indian children. The genetic analysis will help to offer accurate genetic counseling, prenatal diagnosis, and development of mutation-based novel therapeutic strategies.

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Section: Methodsmentioning

confidence: 99%

Seven novel genetic variants in a North Indian cohort with classical homocystinuria

Kaur

Attri

Saini

et al. 2020

Sci Rep

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“…The intra-assay and interassay coecients of variation of normal serum were 3.4% and 12.8% respectively. Serum MMA levels greater than 0.40 umol/l Starczek et al, 1993) were regarded as elevated.…”

Section: Methodsmentioning

confidence: 99%

Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels

Kwok¹,

Tang²,

Woo³

et al. 1998

Int. J. Geriat. Psychiatry

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Background. Low serum cobalamin levels are often found in apparently normal older subjects. A major worry of leaving cobalamin de®ciency untreated is that it may lead to subtle deterioration in cognitive function.Objectives. To investigate the eect of supplementation on the cognitive function of older people with cobalamin de®ciency by a randomized trial.Methods. Fifty Chinese subjects more than 60 years old with serum cobalamin level 5120 pmol/l were randomized into supplement and control groups. Fasting serum methylmalonic acid levels (MMA) were measured. A battery of neuropsychological tests was administered. The supplement group received intramuscular cyanocobalamin injections, while the control group received no intervention. They were followed up at around 4 months.Results. 78% of the subjects had raised MMA, indicating metabolic cobalamin de®ciency. Supplemented subjects improved in performance IQ, but the amount of improvement was not signi®cantly more than that of control subjects. Moreover, the supplement group fared worse than the control group at follow-up in some motor function scores. Three out of seven demented subjects had improvement in Mini-Mental State Examination scores, but there was no consistent improvement in other neuropsychological scores.Conclusions. This study suggested that cobalamin de®ciency did not invariably cause cognitive impairment in older people. There remain the possibilities that cobalamin de®ciency causes cognitive impairment or exacerbates coexisting dementia in some older people. #

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“…The preferred method for analysis has been gas chromatography-mass spectrometry (GC-MS) (5)(6)(7)(8)(9)(10), but GC-MS has the disadvantage of requiring a time-consuming sample preparation step involving either solid-phase extraction (SPE) (7 ) or liquid-liquid extraction (6, 8 -10 ). Silyl derivatization (6,8,10 ) or preparation of alcohol esters (5,7,9 ) is also required, and the turnaround time for GC-MS is typically 15-25 min (5)(6)(7)(8)(9)(10).…”

confidence: 99%

Analysis of Methylmalonic Acid in Plasma by Liquid Chromatography–Tandem Mass Spectrometry

Schmedes¹,

Brandslund

2006

Clinical Chemistry

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Background: Methylmalonic acid (MMA) is a biochemical marker for cobalamin deficiency, particularly in cases where the cobalamin concentration is moderately decreased or in the low-normal range. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization is a rapid, robust method that has been used in MMA analysis. We developed a simple method combining solid-phase extraction (SPE) and derivatization to prepare serum or plasma for LC-MS/MS analysis of MMA.

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Quantification of methylmalonic acid in serum measured by capillary gas chromatography—mass spectrometry as tert.-butyldimethylsilyl derivatives

Cited by 18 publications

References 22 publications

Seven novel genetic variants in a North Indian cohort with classical homocystinuria

Seven novel genetic variants in a North Indian cohort with classical homocystinuria

Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels

Analysis of Methylmalonic Acid in Plasma by Liquid Chromatography–Tandem Mass Spectrometry

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