Urine organic acids

Hyperammonemia also occurs in some organic acidurias, particularly those that affect neonates. Therefore, the urine organic acids should be quantitated in all patients with significant hyperammonemia. 

Figure 3.1.3a shows a normal urine organic acid profile. Panel represents an expansion of the same profile (5% of original abundance) to emphasize the underlying complexity of the urine organic acid fraction and the need to appreciate how informative findings could be hidden within a background of comparable intensity (see section 2.1.8.3). For this reason, exclusive reliance on computer-driven identification is not a safe option because visual evaluation is required, for example in the case of the critical overlaps discussed later in this chapter. 

Acylcarnitine analysis was first performed in urine specimens in the evaluation of patients with organic acidemias. However, because it was found that acylcarnitine analysis of plasma is more informative for the diagnosis of FAO disorders than analysis of urine specimens, plasma has become the preferred specimen [17]. It is only recently that it was shown that urine acylcarnitine analysis still has a role in the diagnostic evaluation of patients with organic acidurias but uninformative or borderline abnormal results of plasma acylcarnitine and urine organic acid analysis [18-21]. In our laboratory, sample preparation and analysis is identical to that of plasma once a urine aliquot has been prepared that is based on the creatinine concentration. 

All enteral feeds were stopped. The baby was given intravenous glucose, L-arginine, sodium benzoate, and sodium phenylacetate. Hemodialysis was initiated. At this time, there were no spontaneous respirations, there was no response to painful stimuli, and brainstem reflexes were absent. The plasma amino acid results revealed a glutamine level of 1500 pmol/L (normal 254-823), and citrulline was undetectable (normal 10-34 pmol/L). Quantitative carnitine, plasma acylcarnitine, and urine organic acid profiles were normal. The urine orotic acid concen-... 

Figure 55-8 Partial urine organic acid profiles 15-23 minute portion of a 33 minute run) of two patients with tyrosinemia type i. A, Acutely III patient with markedly elevated excretion of succiny[acetone, pre-NTBC treatment.The insert shows the selected ion chromatogram of the [M-15] ion of succinylacetone O-TMS-oxime TMS ester, m/z 212 B, Fifteen month old patient, succinylacetone was not detected by either total ion current (orrow) or selected ion chromatogram in three different urine specimens.This patient was later shown to be compound heterozygote for the French Canadian common splice mutation (IVS12+5G>A) and another previously unreported mutation. Peak legend I, Succinylacetone (oxime, peak I) 2, succinylacetone (oxime, peak II) 3, 4-hydroxy phenyllactic acid 4, 4-hydroxy phenylpyruvic add (oxime).The symbol marks the internal standard (pentadecanoic acid), signal abundance is normalized to the intensity of the internal standard peak.

Figure 55-12 Partial urine organic acid profiles (7-28 minute portion of a 33 minute run). A, Ethylmalonic encephalopathy.

The metabolic clinic immediately calls out the results to the provider of the infant, now 9 days old. The baby is in a neonatal intensive care unit due to prematurity but is reportedly doing weU. However, the day the results are reported, the infant is no longer feeding well. The metabolic clinic requests that confirmatory testing of plasma acylcamitine profile and urine organic acid screen be obtained. 

The metabolic team was consulted and obtained STAT biochemical labs including plasma acylcamitine profile, plasma amino acids, urine organic acids, and urine orotic acid. Labs showed elevated orotic acid as well as a plasma amino-acid pattern consistent with ornithine transcarbamylase (OTC) deficiency. The newborn screen was normal. The infant was placed on a protein-restricted diet, supplemented with arginine, and started on nitrogen-scavenging medications. 

Metabolic laboratory tests are specialized tests that are reviewed by a biochemical geneticist and include plasma amino acids and acylcamitines, urine organic acids, and acylglycines that are helpful for pinpointing a metabolic diagnosis and/or monitoring treatment. 

Fig. 8.4 An abnormal urine organic acid profile indicat- acidemia (and organic acid disorder of leucine metabo-...

Laboratory studies Laboratory studies noted a acidosis with a pH of 7.08. The resident calculated an anion gap of 32, which confirmed an anion gap acidosis as the bicarbonate was 6 mmol/L, sodium was 145 nunol/L, and chloride was 107 mmol/L (Box 8.1). Due to the anion gap acidosis, the resident requests both a lactate (which was relatively normal at 2.2 mmol/L) and urine organic acids (Fig. 8.1). 

IVA was initially described in 1966 and became the first organic acidemia described. IVA is caused by a deficiency of the enzyme isovaleryl-CoA dehydrogenase, an enzyme important in leucine catabolism and also important in the transfer of electrons to the respiratory chain [7, 13]. The consequent accumulating metabolites include isovaleric add, isovalerylglydne, 3-hydroxyisovaleric acid, and isovalerylcamitine (C5) [7, 13] (Fig. 17.3). These are easily identified on urine organic acid analysis and acylcamitine profile. The excretion of isovalerylglydne and 3-hydroxyisovaleric acid is diagnostic. 

Acylcamitine profiles indicate elevated long-chain acylcamitines C12, C14, C18, and C18 l, but they also show elevated 3-hydroxyacylcamitines hydroxy-C14, hydroxy-C16, and hydroxy-C 18 1. Urine organic acid analysis shows dicarboxylic acids and 3-hydroxydicarboxylic acids. These latter metabolites can rarely also be observed in certain patients with respiratory chain enzyme deficiencies. Lactate and the lactate to pyruvate ratio are often elevated. The incidence of TCHAD deficiency on newborn screening is estimated at 1 60,000. The diagnosis is usually confirmed by mutation analysis of the genes for the a-chain HADHA and the p-chain HADHB. Enzyme assays are nowadays rarely available. 

Lipid Liver size by examination, serum liver enzyme levels Serum lipid levels (cholesterol, phospholipids, triglycerides), serum glucose, liver size, and fat content by examination and ultrasound, urine organic acids... 

Comparative Gas Chromatographic Analysis of Serum and Urine Organic Acids in the Newborn Before and After Formula Feeding... 

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