In Kazakhstan, the use of MS/MS in metabolic screening programs is in development. This is due to the high cost of equipment and consumables, as well as the lack of special screening centers and specialists.
Selective screening is an important tool for diagnosing various types of inborn errors of metabolism (IEM). Currently, MS/MS-based technologies are widely used, which allow the simultaneous determination of the amount of several metabolites (amino acids, acylcarnitines) from a very small amount of a biological sample. However, age reference cutoff ranges for each analyte should be established first for each population prior to screening as cutoffs depend on various factors such as genetic background, population geographic location, diet, sex, age.
Data on the prevalence of most IEMs, with the exception of phenylketonuria, are not available in Kazakhstan. The data obtained in this study will make it possible to conduct a comparative analysis of the prevalence of IEM in Asia and establish reference values for the concentrations of amino acids and acylcarnitines in the blood of newborns for the Kazakhstan population. Newborn sreening is currently being conducted in Kazakhstan for two hereditary diseases - phenylketonuria and congenital hypothyroidism, which are the most represented screening diseases in most countries. A nationwide newborn screening program for two mandatory diseases, congenital hypothyroidism and phenylketonuria (PKU), began in 2007. ENBS on aminoacid disorders (AAD), organic acidemias (OA) and fatty acid oxidation defects (FAOD) is not conducted in Kazakhstan.
For Kazakhstan, as a country that does not have a mandatory ENBS program, selective screening can be an important tool for diagnosing IEM. The present study aims to develop and validate an MS/MS method for the simultaneous determination of 51 metabolites in DBS for IEM screening, as well as the determination of age-related amino acid ranges, acylcarnitines and succinylacetone in children's population of Kazakhstan. Our selective screening was initiated to obtain data on the incidence of IEM in children at risk in Western Kazakhstan. From October 2022 to December 2024, the frequency of 37 AAD, OA and FAOD will be assessed using LC-MS/MS technology in a group of children at high risk. A summary report will be presented on the screening of high-risk children for IEM in Western Kazakhstan using the LC-MS/MS method.
The results of selective screening tests in different age groups of subjects should be interpreted by comparison with the reference values and/or cut-off levels established for these groups. It is generally accepted that children need to use reference populations that reflect changes associated with growth and development. Therefore, one of the objectives of this study is to establish reference intervals for the concentration of amino acids and acylcarnitines in dry blood spots for different age groups in the range from 1 day to 18 years.
The goal of this observational study is to сonduct selective screening for IEM among children of Kazakhstan aged from 1 day to 18 years using tandem mass spectrometry to determine the prevalence of IEM and reference values of metabolites followed by subsequent substantiation of the need to introduce selective screening of newborns for IEM by MS/MS.
The main questions it aims to answer are:
question 1: what are the reference values of metabolites (amino acids and acylcarnitines) in different age groups of children in Kazakhstan; question 2: what is the contribution of IEM to the structure of the pathology of the nervous system in young children and is it necessary to introduce tandem mass spectrometry technology in the neonatal screening program for IEM?
