Prenatal diagnosis of isovaleric acidemia by fast atom bombardment and tandem mass spectrometry

Shigematsu, Yosuke; Kikawa, Yoshiharu; Sudo, Masakatsu; Kanaoka, Hiroo; Fujioka, Mamoru; Ma, Dan

doi:10.1016/0009-8981(91)90310-9

Cited by 18 publications

(11 citation statements)

References 9 publications

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“…Quantification of both conjugates has suggested a correlation of the metabolite concentrations with genotype, differentiating between groups of patients with a metabolically severe phenotype associated with heterogeneous IVD gene mutations and patients with a metabolically mild or intermediate phenotype associated with one recurring mutation [Ensenauer et al, 2004]. Disease-specific metabolites also accumulate in amniotic fluid during pregnancy with an affected fetus and provide the opportunity for prenatal diagnosis [Hine et al, 1986;Jakobs et al, 1984;Shigematsu et al, 1991].…”

Section: Biochemical Diagonosis and Follow Upmentioning

confidence: 99%

“…a correlation of the metabolite concentrations with genotype, differentiating between groups of patients with a metabolically severe phenotype associated with heterogeneous IVD gene mutations and patients with a metabolically mild or intermediate phenotype associated with one recurring mutation [Ensenauer et al, 2004]. Disease-specific metabolites also accumulate in amniotic fluid during pregnancy with an affected fetus and provide the opportunity for prenatal diagnosis [Jakobs et al, 1984;Hine et al, 1986;Shigematsu et al, 1991]. Several direct and indirect methods to assay IVD activity have been published and, in addition to molecular genetic analysis, can be used to confirm a diagnosis of IVA [Shih et al, 1973;Rhead and Tanaka, 1980;Yoshida et al, 1985;Hyman and Tanaka, 1986;Vockley et al, 1991;Mohsen et al, 1998;Tajima et al, 2005].…”

Section: Biochemical Diagonosis and Follow-upmentioning

confidence: 99%

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Isovaleric acidemia: New aspects of genetic and phenotypic heterogeneity

Vockley

Ensenauer

2006

American J of Med Genetics Pt C

192

161

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Isovaleric acidemia (IVA) is an autosomal recessive inborn error of leucine metabolism caused by a deficiency of the mitochondrial enzyme isovaleryl-CoA dehydrogenase (IVD) resulting in the accumulation of derivatives of isovaleryl-CoA. It was the first organic acidemia recognized in humans and can cause significant morbidity and mortality. Early diagnosis and treatment with a protein restricted diet and supplementation with carnitine and glycine are effective in promoting normal development in severely affected individuals. Both intra-and inter-familial variability have been recognized. Initially, two phenotypes with either an acute neonatal or a chronic intermittent presentation were described. More recently, a third group of individuals with mild biochemical abnormalities who can be asymptomatic have been identified through newborn screening of blood spots by tandem mass spectrometry. IVD is a flavoenzyme that catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA and transfers electrons to the electron transfer flavoprotein. Human IVD has been purified from tissue and recombinant sources and its biochemical and physical properties have been extensively studied. Molecular analysis of the IVD gene from patients with IVA has allowed characterization of different types of mutations in this gene. One missense mutation, 932C>T (A282V), is particularly common in patients identified through newborn screening with mild metabolite elevations and who have remained asymptomatic to date. This mutation leads to a partially active enzyme with altered catalytic properties; however, its effects on clinical outcome and the necessity of therapy are still unknown. A better understanding of the heterogeneity of this disease and the relevance of genotype/phenotype correlations to clinical management of patients are among the challenges remaining in the study of this disorder in the coming years.

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Section: Biochemical Diagonosis and Follow Upmentioning

confidence: 99%

Section: Biochemical Diagonosis and Follow-upmentioning

confidence: 99%

Isovaleric acidemia: New aspects of genetic and phenotypic heterogeneity

Vockley

Ensenauer

2006

American J of Med Genetics Pt C

192

161

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“…Mutation analysis using amniocytes or chorionic villi requires information on the proband, and the contamination of maternal cells may potentially lead to "false negative" results. Two kinds of mass spectrometric methods for prenatal diagnosis have been reported; one is organic acid analysis by the stable-isotope dilution method using GC/MS [3,[6][7][8][9], and the other acylcarnitine analysis using ESI/MS/MS [4,10]. These methods can provide fast results with only a small amount of amniotic fluid.…”

Section: Introductionmentioning

confidence: 99%

Prenatal diagnosis for organic acid disorders using two mass spectrometric methods, gas chromatography mass spectrometry and tandem mass spectrometry

Hasegawa

Iga

Kimura

et al. 2005

Journal of Chromatography B

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“…The FAB-MS-MS system used was a Model TSQ 70 triple stage-quadrupole mass spectrometer (Finnigan MAT Instrument Inc., Tokyo, Japan). The measurement conditions, using the parent scan mode with daughter ion m/z 99 for acylcarnitine measurement or m/z 103 for free carnitine measurement, have been detailed elsewhere (Shigematsu et al 1991;Kodo et al 1989). The quantitation of acylcarnitines was done using calibration lines obtained from measurements of acylcarnitine standards.…”

Section: Carnitine Assay By Fab-ms-msmentioning

confidence: 99%

Acylcarnitine profile in tissues and body fluids of biotin‐deficient rats with and withoutl‐carnitine supplementation

Shigematsu

Bykov

Liu

et al. 1994

J of Inher Metab Disea

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Since biotin-deficient (BD) rats are a good animal model for human multiple carboxylase deficiency and have low plasma free carnitine levels, short-chain acylcarnitine profiles in biotin-deficient rats with L-carnitine supplementation (BDC rats) and BD rats were investigated by fast-atom bombardment and tandem mass spectrometry and gas chromatography/mass spectrometry. By the latter method, 3-hydroxyisovalerylcarnitine was identified in BD rats, and showed the greatest accumulation among short-chain acylcarnitines in tissues of BD rats, while the tissue levels of propionic acid were more markedly elevated than those of 3-hydroxyisovaleric acid. The tissue levels of 3-hydroxyisovaleryl-carnitine were significantly lower and those of propionyl-carnitine were somewhat higher in BDC rats than in BD rats, while the tissue levels of propionic acid and 3-hydroxyisovaleric acid in BDC rats were lower than those in BD rats. These changes were more apparent in kidney than in other tissues. The amounts of urinary excretion of acylcarnitines were markedly larger, and those of 3-hydroxyisovaleric acid were somewhat smaller in BDC rats than in BD rats, while those of propionic acid were very low in BD and BDC rats as compared with those of 3-hydroxyisovaleric acid. It seems that the relationship between the concentrations of 3-hydroxyisovalerylcarnitine and those of propionylcarnitine reflects the unique metabolism of the related metabolites in tissues, especially in kidney, which may be influenced by their urinary excretion and the availability of free carnitine. These data in biotin deficiency suggest that carnitine supplementation is possibly beneficial for patients with holocarboxylase synthetase deficiency who respond incompletely to biotin therapy.

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Prenatal diagnosis of isovaleric acidemia by fast atom bombardment and tandem mass spectrometry

Cited by 18 publications

References 9 publications

Isovaleric acidemia: New aspects of genetic and phenotypic heterogeneity

Isovaleric acidemia: New aspects of genetic and phenotypic heterogeneity

Prenatal diagnosis for organic acid disorders using two mass spectrometric methods, gas chromatography mass spectrometry and tandem mass spectrometry

Acylcarnitine profile in tissues and body fluids of biotin‐deficient rats with and withoutl‐carnitine supplementation

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