In vitro probe acylcarnitine profiling assay using cultured fibroblasts and electrospray ionization tandem mass spectrometry predicts severity of patients with glutaric aciduria type 2

Endo, Mitsuru; Hasegawa, Yuki; Fukuda, Seiji; Kobayashi, Hironori; Yotsumoto, Yuka; Mushimoto, Yuichi; Li, Hong; Purevsuren, Jamiyan; Yamaguchi, Seiji

doi:10.1016/j.jchromb.2010.03.029

Cited by 8 publications

(4 citation statements)

References 19 publications

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“…Several laboratory studies can be used to characterize MADD‐patients, including urine organic acid analysis, plasma acylcarnitine profiling, and ultimately molecular studies to pinpoint the genetic defect . Unfortunately, prognostic biomarkers that may predict disease severity are not available.…”

Section: Introductionmentioning

confidence: 99%

“…2,7,8 Several laboratory studies can be used to characterize MADD-patients, including urine organic acid analysis, plasma acylcarnitine profiling, and ultimately molecular studies to pinpoint the genetic defect. 2,9,10 Unfortunately, prognostic biomarkers that may predict disease severity are not available. In fibroblasts, FAO flux activities provide an estimate of the rate of mitochondrial FAO, whereas acylcarnitine profiling improves insight on both the site and the severity of the enzymatic block.…”

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confidence: 99%

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Prediction of disease severity in multiple acyl‐CoA dehydrogenase deficiency: A retrospective and laboratory cohort study

Rijt

Ferdinandusse

Giannopoulos

et al. 2019

J of Inher Metab Disea

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Summary Multiple acyl‐CoA dehydrogenase deficiency (MADD) is an ultra‐rare inborn error of mitochondrial fatty acid oxidation (FAO) and amino acid metabolism. Individual phenotypes and treatment response can vary markedly. We aimed to identify markers that predict MADD phenotypes. We performed a retrospective nationwide cohort study; then developed an MADD‐disease severity scoring system (MADD‐DS3) based on signs and symptoms with weighed expert opinions; and finally correlated phenotypes and MADD‐DS3 scores to FAO flux (oleate and myristate oxidation rates) and acylcarnitine profiles after palmitate loading in fibroblasts. Eighteen patients, diagnosed between 1989 and 2014, were identified. The MADD‐DS3 entails enumeration of eight domain scores, which are calculated by averaging the relevant symptom scores. Lifetime MADD‐DS3 scores of patients in our cohort ranged from 0 to 29. FAO flux and [U‐13C]C2‐, C5‐, and [U‐13C]C16‐acylcarnitines were identified as key variables that discriminated neonatal from later onset patients (all P < .05) and strongly correlated to MADD‐DS3 scores (oleate: r = −.86; myristate: r = −.91; [U‐13C]C2‐acylcarnitine: r = −.96; C5‐acylcarnitine: r = .97; [U‐13C]C16‐acylcarnitine: r = .98, all P < .01). Functional studies in fibroblasts were found to differentiate between neonatal and later onset MADD‐patients and were correlated to MADD‐DS3 scores. Our data may improve early prediction of disease severity in order to start (preventive) and follow‐up treatment appropriately. This is especially relevant in view of the inclusion of MADD in population newborn screening programs.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Prediction of disease severity in multiple acyl‐CoA dehydrogenase deficiency: A retrospective and laboratory cohort study

Rijt

Ferdinandusse

Giannopoulos

et al. 2019

J of Inher Metab Disea

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show abstract

“…In vitro probe acylcarnitine assay using cultured fibroblasts facilitates the identification of the severity of the disorder. 12 In our patient, biochemical markers were frequently analyzed, and a large intraindividual variation for each marker was observed. One of the reasons could be the lack of standardization (time of the day and nutritional status).…”

Section: Discussionmentioning

confidence: 78%

Favorable Outcome After Physiologic Dose of Sodium-d,l-3-Hydroxybutyrate in Severe MADD

Rijt¹,

Heiner‐Fokkema

Sarvaas

et al. 2014

Pediatrics

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Multiple acyl coenzyme A dehydrogenase deficiency (MADD) is a severe inborn error of metabolism. Experiences with sodium-D,L-3-hydroxybutyrate (3-HB) treatment are limited although positive; however, the general view on outcome of severely affected patients with MADD is relatively pessimistic. Here we present an infant with MADD in whom the previously reported dose of 3-HB did not prevent the acute, severe, metabolic decompensation or progressive cardiomyopathy in the subsequent months. Only after a physiologic dose of 2600 mg/kg of 3-HB per day were ketone bodies detected in blood associated with improvement of the clinical course, N-terminal prohormone of brain natriuretic peptide and echocardiographic parameters. Long-term studies are warranted on 3-HB treatment in patients with MADD.

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“…D. Western blot analyses of proteins in the patient's fibroblasts. The patient's fibroblasts were prepared as described previously [5,11]. For analysis of ETFDH, ETFα, and ETFβ, 25 μg of protein was applied to the gel.…”

Section: Case Reportmentioning

confidence: 99%

Amelioration of acylcarnitine profile using bezafibrate and riboflavin in a case of adult-onset glutaric acidemia type 2 with novel mutations of the electron transfer flavoprotein dehydrogenase (ETFDH) gene

Shioya¹,

Takuma²,

Yamaguchi³

et al. 2014

Journal of the Neurological Sciences

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In vitro probe acylcarnitine profiling assay using cultured fibroblasts and electrospray ionization tandem mass spectrometry predicts severity of patients with glutaric aciduria type 2

Cited by 8 publications

References 19 publications

Prediction of disease severity in multiple acyl‐CoA dehydrogenase deficiency: A retrospective and laboratory cohort study

Prediction of disease severity in multiple acyl‐CoA dehydrogenase deficiency: A retrospective and laboratory cohort study

Favorable Outcome After Physiologic Dose of Sodium-d,l-3-Hydroxybutyrate in Severe MADD

Amelioration of acylcarnitine profile using bezafibrate and riboflavin in a case of adult-onset glutaric acidemia type 2 with novel mutations of the electron transfer flavoprotein dehydrogenase (ETFDH) gene

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