Age-Specific Reference Values for Free Carnitine and Short Chain Acylcarnitines Content in Dried Blood Spots in Newborns in Western Kazakhstan: A Tandem Mass Spectrometry Measurement

Abstract

Sodium-dependent multivitamin transporter (SMVT) deficiency is a recently described multivitamindependent inherited metabolic disorder (IMD). SMVT is encoded by the SLC5A6 gene located on chromosome 2p23.3. We describe a clinical case of SMVT deficiency in a child with developmental delay, microcephaly, persistent neurological symptoms, skin lesions and frequent upper respiratory tract infections. A tandem mass spectrometry study of the metabolic profile of amino acids and acylcarnitines, carried out twice, showed increased blood levels of methylmalonylcarnitine + 3-hydroxyisovalerylcarnitine (C4DC/C5OH). Urine analysis by gas chromatography-mass spectrometry showed persistently increased excretion of 3-OH-isovaleric acid. The combination of increased blood concentrations of C4DC/C5OH and increased urinary excretion of 3-OHisovaleric acid suggested a metabolic disorder associated with impaired biotin metabolism. Determination of the level of biotinidase in the blood did not reveal deviations from the reference values. Biotin was prescribed. As a result of clinical exome sequencing, complex heterozygous variants of the SLC5A6 gene encoding SMVT were identified. The patient was treated with increased doses of oral biotin, pantothenic acid, and lipoic acid, which resulted in significant clinical improvement.This study aims to explore the effectiveness of education and campaign approaches in building public awareness about the importance of preventing stunting in future generations. Employing a qualitative descriptive study approach, the researcher engaged three informants with relevant experience and knowledge in the field of child health and stunting prevention. Through in-depth interviews and content analysis, this study describes the perceptions, understandings, and experiences of informants regarding the education and campaign efforts conducted to prevent stunting. The results reveal a variety of strategies employed, including direct counselling, provision of educational materials, social media campaigns, and community activities. Data analysis underscores challenges encountered in implementing the program, such as low levels of community participation, limited access to health services, and financial constraints. Nonetheless, the findings also identify opportunities to enhance the program's effectiveness, such as collaboration with community institutions and a culturally nuanced approach. This research offers valuable insights for the development of more effective strategies to cultivate community awareness about stunting and foster positive behavior change to prevent stunting in future generations. In conclusion, education and campaigns play a pivotal role in stunting prevention efforts, but sustained and coordinated endeavors are requisite to achieve substantial impact.Education for Sustainable Development (ESD) gives learners the knowledge, skills, values and behavior to face the global challenges. ESD offers countries to develop and expand educational activities that focus on sustainability issues. Green school is one of the initiatives that introduce global challenges to schools such as climate change, water, biodiversity, the oceans, sustainable urbanization, disaster risk reduction, and sustainable lifestyles through education. The research aims to describe the implementation of integrated green school in Bandung public school as an initiative to introduce sustainability through education. Descriptive qualitative method is used in this research. Observations and interviews were conducted to principal, teachers, students, and other parts of the school community. Literature study was also conducted to compare the implementation of Bandung green school to other schools in sustainability. The result showed that Bandung integrated green school has the whole-school approach to sustainability than non- green school. There are 20 programs implemented by Bandung green school by integrating them to the whole school community. Integrated green school initiative led the school to introduce sustainability through education.Measuring the level of acylcarnitines and free carnitine in the blood is one of the stages of early diagnosis of inborn errors of metabolism, including disorders of fatty acid oxidation, and ensures timely initiation of therapeutic measures. Currently, tandem mass spectrometry (MS/MS) is successfully used for these purposes. Dried blood spot acylcarnitine reference values developed for neonates are critical for interpreting test results and diagnosing fatty acid metabolic disorders. Objectives: To establish reference values for the concentrations of free carnitine and short-chain acylcarnitines in samples of dried blood spots of newborns in Western Kazakhstan using LC-MS/MS technology (liquid chromatography-tandem mass spectrometry). Methods: The cross-sectional study included 250 healthy newborns from Western Kazakhstan aged 1-3 days, born at term and breastfed, 49.2% boys and 50.2% girls. To establish age reference values for C0 and shortchain acylcarnitines, newborns were divided into three groups (1) 1-day, (2) 2-day and (3) 3-day. Guthrie blood samples were collected on days 1–3 of life and quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Nonparametric statistical approaches were used to obtain percentile distributions for newborns ranging from 2.5 to 97.5. Results: A statistically significant difference was found in the mean levels of acetylcarnitine (C2), butyrylcarnitine (C4) and tiglylcarnitine (C5:1) in men and women. The highest values were determined in the female group. Age-related differences were observed in the concentration levels of malonylcarnitine (C3DC), butyrylcarnitine (C4), isovalerylcarnitine (C5) and glutarylcarnitine (C5DC). No significant correlations were found between the content of C0 and 10 short-chain acetylcarnitines in dried blood spots and the body weight of newborns. Conclusion: The present study established concentrations of acylcarnitines and free carnitine that can be used as reference standards in a newborn screening program for inherited metabolic diseases in Kazakhstan.