Amino and organic acid analysis: Essential tools in the diagnosis of inborn errors of metabolism

Phipps, William S.; Jones, Peter M.; Patel, Khushbu

doi:10.1016/bs.acc.2019.04.001

Cited by 16 publications

(12 citation statements)

References 74 publications

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“…Third, deproteinization of serum was not performed until after freezing and just prior to analysis within 2 weeks of collection. Deproteinization prevents losing AA by co-precipitation with other serum proteins, therefore this may have impacted our results, especially for sulfur-containing AAs (methionine, taurine) [44]. However, all samples were handled similarly, so any effect should have been standardized across all samples.…”

Section: Discussionmentioning

confidence: 99%

Serum and Fecal Amino Acid Profiles in Cats with Chronic Kidney Disease

Summers

Quimby

Blake³

et al. 2022

Veterinary Sciences

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The purpose of the study was to quantify serum and fecal amino acids (AA) in cats with chronic kidney disease (CKD) and compare to healthy cats. Thirty-five cats with International Renal Interest Society Stage 1–4 CKD and 16 healthy mature adult and senior client-owned cats were included in this prospective cross-sectional study. Sera were analyzed for 25 AA concentrations using an ion exchange chromatography AA analyzer with post column ninhydrin derivatization. Voided fecal samples were analyzed for 22 AA concentrations using liquid chromatography with tandem mass spectrometry. CKD cats had lower serum concentrations of phenylalanine (mean difference ± standard error of the mean: 12.7 ± 4.3 µM; p = 0.03), threonine (29.6 ± 9.2 µM; p = 0.03), tryptophan (18.4 ± 5.4 µM; p = 0.005), serine (29.8 ± 12.6 µM; p = 0.03), and tyrosine (11.6 ± 3.8 µM; p = 0.01) and higher serum concentrations of aspartic acid (4.7 ± 2.0 µM; p = 0.01), β-alanine (3.4 ± 1.2 µM; p = 0.01), citrulline (5.7 ± 1.6 µM; p = 0.01), and taurine (109.9 ± 29.6 µM; p = 0.01) when compared to healthy cats. Fecal AA concentrations did not differ between healthy cats and CKD cats. 3-Methylhistidine-to-creatinine did not differ between healthy cats with and without muscle loss. Cats with CKD IRIS Stages 1–4 have a deranged serum amino acid profile compared to healthy cats.

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Section: Discussionmentioning

confidence: 99%

Serum and Fecal Amino Acid Profiles in Cats with Chronic Kidney Disease

Summers

Quimby

Blake³

et al. 2022

Veterinary Sciences

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“…Urine organic acid analysis serves as a vital tool for the diagnosis and treatment of inborn errors of metabolism (IEM) [ 1 ]. It is well established that discrete IEMs give rise to signature organic acids that are detectable by gas chromatography–mass spectrometry (GC-MS) [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Diversion of Acetyl CoA to 3-Methylglutaconic Acid Caused by Discrete Inborn Errors of Metabolism

2022

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A growing number of inborn errors of metabolism (IEM) have been identified that manifest 3-methylglutaconic (3MGC) aciduria as a phenotypic feature. In primary 3MGC aciduria, IEM-dependent deficiencies in leucine pathway enzymes prevent catabolism of trans-3MGC CoA. Consequently, this metabolite is converted to 3MGC acid and excreted in urine. In secondary 3MGC aciduria, however, no leucine metabolism pathway enzyme deficiencies exist. These IEMs affect mitochondrial membrane structure, electron transport chain function or ATP synthase subunits. As a result, acetyl CoA oxidation via the TCA cycle slows and acetyl CoA is diverted to trans-3MGC CoA, and then to 3MGC acid. Whereas the trans diastereomer of 3MGC CoA is the only biologically relevant diastereomer, the urine of affected subjects contains both cis- and trans-3MGC acids. Studies have revealed that trans-3MGC CoA is susceptible to isomerization to cis-3MGC CoA. Once formed, cis-3MGC CoA undergoes intramolecular cyclization, forming an anhydride that, upon hydrolysis, yields cis-3MGC acid. Alternatively, cis-3MGC anhydride can acylate protein lysine side chains. Once formed, cis-3MGCylated proteins can be deacylated by the NAD+-dependent enzyme, sirtuin 4. Taken together, the excretion of 3MGC acid in secondary 3MGC aciduria represents a barometer of defective mitochondrial function.

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“…Such findings have been observed using different samples (urine, plasma, serum, dried blood spots and faeces) and technical approximations including LC-MS, NMR, GC-MS among others [ 15 , 16 ]. In the diagnostic scenario of OA are evaluated in urine using GC-MS with a protocol that allows the simultaneous evaluation of the above mentioned metabolites [ 21 , 22 , 23 ]. Using this methodology, studies related to the impact of dietary habits on the urinary OA profile in newborns are limited, although there are some reports regarding the normal profile in this population [ 12 , 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%