Proton NMR spectroscopic analysis of multiple acyl-CoA dehydrogenase deficiency—capacity of the choline oxidation pathway for methylation in vivo

Burns, Shamus P.; Holmes, Heather C.; Chalmers, R. A.; Johnson, Andrew; Iles, Richard A.

doi:10.1016/s0925-4439(98)00015-5

Cited by 14 publications

(9 citation statements)

References 23 publications

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“…In one other patient in whom riboflavin therapy was started during severe metabolic decompensation fatal outcome could not be prevented [[16]]. Only one patient was reported to be clearly unresponsive to riboflavin [[17]].…”

Section: Resultsmentioning

confidence: 99%

Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency

Grünert

2014

Orphanet J Rare Dis

157

156

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BackgroundMultiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder caused by deficiency of electron transfer flavoprotein or electron transfer flavoprotein dehydrogenase. The clinical picture of late-onset forms is highly variable with symptoms ranging from acute metabolic decompensations to chronic, mainly muscular problems or even asymptomatic cases.MethodsAll 350 cases of late-onset MADD reported in the literature to date have been analyzed and evaluated with respect to age at presentation, diagnostic delay, biochemical features and diagnostic parameters as well as response to treatment.ResultsMean age at onset was 19.2 years. The mean delay between onset of symptoms and diagnosis was 3.9 years. Chronic muscular symptoms were more than twice as common as acute metabolic decompensations (85% versus 33% of patients, respectively). 20% had both acute and chronic symptoms. 5% of patients had died at a mean age of 5.8 years, while 3% of patients have remained asymptomatic until a maximum age of 14 years. Diagnosis may be difficult as a relevant number of patients do not display typical biochemical patterns of urine organic acids and blood acylcarnitines during times of wellbeing. The vast majority of patients carry mutations in the ETFDH gene (93%), while mutations in the ETFA (5%) and ETFB (2%) genes are the exceptions. Almost all patients with late-onset MADD (98%) are clearly responsive to riboflavin.ConclusionsLate-onset MADD is probably an underdiagnosed disease and should be considered in all patients with acute or chronic muscular symptoms or acute metabolic decompensation with hypoglycemia, acidosis, encephalopathy and hepatopathy. This may not only prevent patients from invasive diagnostic procedures such as muscle biopsies, but also help to avoid fatal metabolic decompensations.

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Section: Resultsmentioning

confidence: 99%

Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency

Grünert

2014

Orphanet J Rare Dis

157

156

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“…An increase of this betaine/creatinine ratio over the first 7 days of life was repeatedly observed and accorded to a higher total excretion of betaine [26][27][28][29][30]. Davies et al [26] reported a significant increase of the urine betaine/creatinine ratio in this time period.…”

Section: Discussionmentioning

confidence: 99%

1H-NMR metabolic profiling of human neonatal urine

Trump

Laudi²,

Unruh

et al. 2006

Magn Reson Mater Phy

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“…Many reports on this topic have been published (1)(2)(3)(4)(5). Several inborn errors in the pyrimidine metabolism are known.…”

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confidence: 99%

β‐Ureidopropionase deficiency: A novel inborn error of metabolism discovered using NMR spectroscopy on urine

et al. 2001

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In this work, NMR investigations that led to the discovery of a new inborn error of metabolism, ␤-ureidopropionase (UP) deficiency, are reported. 1D 1 H-NMR experiments were performed using a patient's urine. 3-Ureidopropionic acid was observed in elevated concentrations in the urine spectrum. A 1D 1 H-1 H total correlation spectroscopy (TOCSY) and two heteronuclear 2D NMR techniques (heteronuclear multiple bond correlation (HMBC) and heteronuclear single-quantum correlation (HSQC)) were used to identify the molecular structure of the compound that caused an unknown doublet resonance at 1.13 ppm. Combining the information from the various NMR spectra, this resonance could be assigned to 3-ureidoisobutyric acid. These observations suggested a deficiency of UP. With 1D 1 H-NMR spectroscopy, UP deficiency can be easily diagnosed. The 1 H-NMR spectrum can also be used to diagnose patients suffering from other inborn errors of metabolism in the pyrimidine degradation pathway.

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Proton NMR spectroscopic analysis of multiple acyl-CoA dehydrogenase deficiency—capacity of the choline oxidation pathway for methylation in vivo

Cited by 14 publications

References 23 publications

Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency

Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency

1H-NMR metabolic profiling of human neonatal urine

β‐Ureidopropionase deficiency: A novel inborn error of metabolism discovered using NMR spectroscopy on urine

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