Evaluation of mass spectrometric indicators for the differential diagnosis of inherited disorders of organic acid metabolism in children

The objective. To calculate the reference intervals of the content of organic acids in the urine of the children of different age groups based on the results of gas chromatography with mass spectrometry; to find out their diagnostic value as biochemical markers of organic acidemia and other metabolic disorders.

Materials and methods. The group consisted of 80 children with suspected organic acidemia. The control group consisted of 443 practically healthy children of different ages. The urine samples were analyzed for the content of 28 organic by gas chromatography with mass spectrometry.

The results. The authors established reference intervals of 28 organic urine acids. The differences in the reference intervals defined in this work were isolated from those obtained in other studies. There were identified 37 children with abnormalities in the spectrum of organic acids according to the results of the analysis of the urine samples of patients by gas chromatography-mass spectrometry. 23 patients were diagnosed with various forms of organic acidemia on the basis of characteristic clinical and laboratory data and changes in the indicators of organic acids.

The conclusion. The method of gas chromatography with mass spectrometry has proved its effectiveness  and reliability for the diagnosis of hereditary diseases from the group of organic acidemias.

1. Ozand P.T., Gascon G.G. Organic acidurias: a review. Part 1. J. Child Neurol 1991; 6(3): 197–219. DOI: 10.1177/088307389100600302

2. Scriver C.R., Beaudet A.L., Sly W.S., Childs B., Valle D., Kinzler W. et al. The Metabolic and Molecular Basis of Inherited Disease. Part 9, Organic Acids. 8th ed. New York, NY: McGraw-Hill, Inc., 2001; 2109–2260.

3. Lord R.S., Bralley J.A. Laboratory evaluations for integrative and functional medicine. 2nd edition, Metametrix Institute 2008; 179.

4. Kazantseva L.Z., Antoshechkin A.G., Nikolaeva E.A. Clinical and biochemical diagnosis of hereditary forms of organic acidemia in children. Materinstvo i detstvo 1992; 2–3: 21–25. (in Russ)

5. Pawar C., Rao P., Lewis L., Moorkoth S. Development of a GC-MS bio-analytical method to detect organic academia in neonatal/paediatric urine sample. Int J Pharmacy Technol 2016; 2: 13110–13124.

6. Kuhara T. Gas chromatographic-mass spectrometric urinary metabolome analysis to study mutations of inborn errors of metabolism. Mass Spectrom Rev 2005; 24: 8141–827. DOI: 10.1002/mas.20038

7. Jiang M., Liu L., Mei H., Li X., Cheng J., Cai Y. Detection of inborn errors of metabolism using GC-MS: over 3 years of experience in southern China. J Pediatr Endocrinol Metab 2015; 28: 375–380. DOI: 10.1515/jpem-2014-0164

8. Christou C.K., Gika H.G., Raikos N., Theodoridis G.A. GC-MS analysis of organic acids in human urine in clinical settings: A study of derivatization and other analytical parameters. J Chromatography B 2014; 964: 195–201. DOI: 10.1016/j.jchromb.2013.12.038.

9. Metagene. Metabolic and genetic information center. http://www.metagene.de/index.html. Ссылка активна на 21.11.2018.