Selective screening for inborn errors of metabolism using tandem mass spectrometry in West Kazakhstan children: study protocol

Gulmira Zharmakhanova; Victoria Kononets; Saule Balmagambetova; Lyazzat Syrlybayeva; Eleonora Nurbaulina; Zhanna Zhussupova; Svetlana Sakhanova; Dinmukhamed Ayaganov; Svetlana Kim; Akmaral Zhumalina

doi:10.3389/fgene.2023.1278750

Selective screening for inborn errors of metabolism using tandem mass spectrometry in West Kazakhstan children: study protocol

Front Genet. 2024 Jan 12:14:1278750. doi: 10.3389/fgene.2023.1278750. eCollection 2023.

Affiliations

¹ Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.
² Department of Oncology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.
³ Department of General Medical Practice, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.
⁴ Aktobe Regional Tertiary Care Center, Department of Neonatal Pathology, Aktobe, Kazakhstan.
⁵ Scientific-Practical Center, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.
⁶ Department of Neurology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.
⁷ Department of Children's Diseases No. 2, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.
⁸ Department of Children's Diseases No. 1 with Neonatology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.

Abstract

Data on the prevalence of most inborn errors of metabolism are still unavailable in Kazakhstan. The study aims to perform selective screening for hereditary metabolic diseases among patients aged from 1 day to 18 years in western Kazakhstan using the LC-MS/MS method, with establishing the reference values for the content of amino acids, acylcarnitines, and succinylacetone in blood samples of healthy children. Tasks: 1. To assess the burden of metabolic disorders detected by LC-MS/MS in western Kazakhstan by examination of children at clinical risk in pediatric clinics throughout the region; https://www.frontiersin.org/register?returnUrl=https://loop.frontiersin.org 2. To set the reference values of metabolites in the child population; 3. To analyze the age distribution, prevalence, and age of onset for each identified IEM, further comparing the obtained findings with those from previously published reports in other populations.

Methods: To set the reference values of 51 metabolites in the child population, 750 healthy children will be included. The selective screening will be performed among 1,500 patients aged 1 day to 18 years with suspected hereditary metabolic disorders.

Anticipated results: The results of selective screening will be interpreted by comparison with the reference values established. Diagnosis will be based on clinical signs, blood levels of amino acids, acylcarnitines, succinylacetone, and urine levels of organic acids and tests for gene mutations. An assessment of 37 inborn errors of metabolism frequencies in high-risk children will be performed. The research will further develop the national as selective as expanded newborn screening programs. The study was registered in clinicaltrials. gov (https://www.

Clinicaltrials: gov/study/NCT05910151) on 16 June 2023.

Keywords: Kazakhstan; acylcarnitines; amino acids; inborn errors of metabolism; selective screening; succinylacetone; tandem mass spectrometry.

Associated data

ClinicalTrials.gov/NCT05910151

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan, grant No. AP14869996.