Glutaric aciduria type II: Report on a previously undescribed metabolic disorder

Przyrembel, Hildegard; Wendel, U.; Becker, Kathrin; Bremer, H. J.; Bruinvis, L.; Ketting, D.; Wadman, S.K.

doi:10.1016/0009-8981(76)90060-7

Cited by 214 publications

(107 citation statements)

References 40 publications

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“…All the FAD-dependent acyl CoA dehydrogenases, including these three and isovaleryl, methylbutyryl, isobutyryl, and glutaryl CoA dehydrogenases require two proteins in common for electron transport from the reduced acyl CoA dehydrogenases to coenzyme Q in the electron transport chain: the electron transferring flavoprotein (ETF) and the iron sulfur flavoprotein (ETF dehydrogenase) (18,33). In inherited glutaric aciduria type I1 (GAII) there appears to be a generalized defect in all the FAD-dependent acyl CoA dehydrogenases as reasoned from the pattern of the urinary organic acids (13,31,34) and the demonstration of defective oxidation of leucine, isoleucine, valine, lysine, and butyrate in cultured fibroblasts (22,31,32). A combined defect in so many dehydrogenases could result from a defect either in protein necessary for their activity or in a cofactor common to each (13,31,32).…”

Section: Discussionmentioning

confidence: 99%

“…In inherited glutaric aciduria type I1 (GAII) there appears to be a generalized defect in all the FAD-dependent acyl CoA dehydrogenases as reasoned from the pattern of the urinary organic acids (13,31,34) and the demonstration of defective oxidation of leucine, isoleucine, valine, lysine, and butyrate in cultured fibroblasts (22,31,32). A combined defect in so many dehydrogenases could result from a defect either in protein necessary for their activity or in a cofactor common to each (13,31,32). Moreover there is some evidence that GAII is an heterogeneous disorder (8).…”

Section: Discussionmentioning

confidence: 99%

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Oxidation of Fatty Acids in Cultured Fibroblasts: a Model System for the Detection and Study of Defects in Oxidation

et al. 1982

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Oxidation of Fatty Acids in Cultured Fibroblasts: a Model System for the Detection and Study of Defects in Oxidation

et al. 1982

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“…Plasma acylcarnitine profiles show an increase of all chain-length acylcarnitines, while urine organic acid profiles display high concentrations of glutaric, 2-hydroxyglutaric, ethylmalonic and other dicarboxylic acids, and several glycine derivatives (Frerman and Goodman 2001). Early studies reported that a marked increase of plasma proline is common in neonatal-onset patients (Frerman and Goodman 2001;Goodman et al 1983;Przyrembel et al 1976;Sweetman et al 1980), but plasma amino acid analysis does not usually play a part in the diagnostic workup.…”

Section: Introductionmentioning

confidence: 99%

Hyperprolinemia in Type 2 Glutaric Aciduria and MADD-Like Profiles

et al. 2015

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Classical neonatal-onset glutaric aciduria type 2 (MAD deficiency) is a severe disorder of mitochondrial fatty acid oxidation associated with poor survival. Secondary dysfunction of acyl-CoA dehydrogenases may result from deficiency for riboflavin transporters, leading to severe disorders that, nevertheless, are treatable by riboflavin supplementation. In the last 10 years, we identified nine newborns with biochemical features consistent with MAD deficiency, only four of whom survived past the neonatal period. A likely iatrogenic cause of riboflavin deficiency was found in two premature newborns having parenteral nutrition, one of whom recovered upon multivitamin supplementation, whereas the other died before diagnosis.Four other patients had demonstrated mutations involving ETF or ETF-DH flavoproteins, whereas the remaining three patients presumably had secondary deficiencies of unknown mechanism. Interestingly, six newborns among the seven tested for plasma amino acids had pronounced hyperprolinemia. In one case, because the initial diagnostic workup did not include organic acids and acylcarnitine profiling, clinical presentation and hyperprolinemia suggested the diagnosis. Analysis of our full cohort of >50,000 samples from >30,000 patients suggests that the proline/ alanine ratio may be a good marker of MAD deficiency and could contribute to a more effective management of the treatable forms.

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“…Defective fatty acid oxidation as well as amino acid degradation led to accumulation of GA, lactate, and dicarboxylic acids such as ethylmalonate and adipate [6]. Two other clinical entities, both affecting the nervous system, are characterized by accumulation of D-and L-2-hydroxyglutaric acids (D-2OHGA, L-2OHGA), respectively, in tissues and body fluids [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Organic anion transporters OAT1 and OAT4 mediate the high affinity transport of glutarate derivatives accumulating in patients with glutaric acidurias

Hagos

Krick

Braulke

et al. 2008

Pflugers Arch - Eur J Physiol

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Glutaric acidurias are rare inherited neurodegenerative disorders accompanied by accumulation of the metabolites glutarate (GA) and 3-hydroxyglutarate (3OHGA), glutaconate, L-, or D-2-hydroxyglutarate (L-2OHGA, in all body fluids. Oocytes expressing the human (h) sodium-dicarboxylate cotransporter (NaDC3) showed sodium-dependent inward currents mediated by GA, 3OHGA, L-, and D-2OHGA. The organic anion transporters (OATs) were examined as additional transporters for GA derivatives. The uptake of [ 3 H]p-aminohippurate in hOAT1-transfected human embryonic kidney (HEK293) cells was inhibited by GA, 3OHGA, D-, or L-2OHGA in a concentration-dependent manner. None of these compounds affected the hOAT3-mediated uptake of [ 3 H]estrone sulfate (ES). In hOAT4-expressing cells and oocytes, ES uptake was strongly increased by intracellular GA derivatives. The data provide a model for the concerted action of OAT1 and NaDC3 mediating the basolateral uptake, and OAT4 mediating apical secretion of GA derivatives from proximal tubule cells and therefore contribute to the renal clearance of these compounds.

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Glutaric aciduria type II: Report on a previously undescribed metabolic disorder

Cited by 214 publications

References 40 publications

Oxidation of Fatty Acids in Cultured Fibroblasts: a Model System for the Detection and Study of Defects in Oxidation

Oxidation of Fatty Acids in Cultured Fibroblasts: a Model System for the Detection and Study of Defects in Oxidation

Hyperprolinemia in Type 2 Glutaric Aciduria and MADD-Like Profiles

Organic anion transporters OAT1 and OAT4 mediate the high affinity transport of glutarate derivatives accumulating in patients with glutaric acidurias

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