Normal urine organic acid profile

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. 

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.

The inability to form ketone bodies as a result of 3-hydroxy-3-methyl-glutaryl-CoA synthase deficiency (HMGS, 14.12) leads to hypoketotic hypoglycemia with unusually high plasma free fatty acid levels. Urine organic acid profiles are non-descript, the plasma acylcarnitine pattern is normal. Thus far only four patients were reported at ages between 1 and 6 years their outcome was favourable. Mutations were found in most alleles [16]. 

Fig. 11.10 Chromatogram of organic acids extracted using DEAE-Sephadex from the urine of the same patient described in the legend to Fig. 11.9, after 1 year on vitamin B12 therapy. Separated as described for Fig. 11.9. Peak identifications are given in the legend to Fig. 11.9, additional identifications are 10, 2-deoxytetronate 17,4-hydroxyphenyl-acetate 18, 2-deoxypentonate. The reduced excretion of methylmalonate and the abolition of methylcitrate and 3-hydroxypropionate excretion together with the production of an otherwise normal urinary organic acid profile is apparent when compared to Fig. 11.9. (The horizontal axis represents the time elapsed in minutes from sample injection.) (Redrawn from the original, after Chalmers, 1980)...

A volume equivalent to 0.25 mg of creatinine from 500 mL of urine of a healthy adult donor is analyzed to exclude unusual findings or presence of drugs and/or other interfering compounds in the organic acid profile. If the specimen is deemed free of interference and suitable to be used as a QC normal control, the collection is diluted with RO water so that 3 ml equals 0.25 mg creatinine equivalent, and aliquoted into screw-cap vials during continued mixing then stored frozen. 

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. 

Table 7.2 Urinary organic acids identified during metabolic profiling by GC-MS of normal urine (from Homing and Horning, 1971a,b).

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