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Medium-chain acyl-CoA dehydrogenase deficiency in North Macedonia – ten years experience

  • Violeta Anastasovska ORCID logo EMAIL logo , Mirjana Kocova ORCID logo , Nikolina Zdraveska ORCID logo , Tine Tesovnik ORCID logo , Maruša Debeljak ORCID logo and Jernej Kovač ORCID logo
Published/Copyright: March 3, 2025
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 5

Abstract

Objectives

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessive disorder of fatty acid oxidation, with potentialy fatal outcome. Early diagnosis of MCADD by acylcarnitine analysis on newborn screening using tandem mass spectrometry can potentially reduce morbidity and mortality. In this study, we evaluate the prevalence and genetic background of MCADD in North Macedonia.

Methods

Medium chain length acylcarnitines, were measured on newborn screening blood spot cards by tandem mass spectrometry. The molecular diagnosis was performed by whole exome sequencing of the ACADM gene, and detected mutations were confirmed with Sanger sequencing in all neonates with positive MCAD screening markers, and their parents as well.

Results

A total of 52,942 newborns were covered by metabolic screening during the period May 2014–May 2024. 11 unrelated Macedonian neonates were detected with positive MCADD screening markers, and prevalence of 1/4,813 live births was estimated. Molecular analysis of the ACADM gene showed that c.985A>G was the most prevalent mutation occurred on 77.27 % of the alleles, while 18.18 % alleles carried c.244dupT pathogenic variant. Seven patients were homozygous for c.985A>G (63.6 %) while one was homozygous for c.244dupT (9.1 %) variant. Two patients were compound heterozygotes with c.985A>G/c.244dupT genotype (18.2 %), and one patient had c.985A>G allele without detection of the second ACADM mutant allele.

Conclusions

The NBS estimated prevalence of MCADD in Macedonian population was more frequent than in the other European population and worldwide incidence in general. This is the first report of the genetic background of MCADD in North Macedonia.

Keywords: ACADM mutations; fatty acid oxidation disorder; medium-chain acyl-CoA dehydrogenase deficiency; neonatal screening
Corresponding author: Violeta Anastasovska, Department of Neontal Screening, Faculty of Medicine, University Clinic for Pediatrics, Ss. Cyril and Methodius University in Skopje, Vodnjanska 17, 1000, Skopje, Republic of North Macedonia, E-mail:

Acknowledgments

We would like to thank the children and their parents who participated in this study.

  1. Research ethics: This study was approved by the Ethics Committee of the University Clinic for Pediatrics in Skopje.

  2. Informed consent: Informed consent for molecular analysis was obtained from all individuals included in this study.

  3. Author contributions: VA carried out the screening for inborn errors of metabolism in the country, performed the retrospective evaluation of the data, the designing, writing, and editing of the manuscript. MK and NZ were instrumental in the editing of the manuscript, they treated, and followed babies and children with MCAD. TT, MD, and JK performed the molecular analysis of ACADM gene, and interpretation of the NGS results as well as contributed in the editing of the manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: Not applicable.

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Received: 2024-11-08
Accepted: 2025-02-13
Published Online: 2025-03-03
Published in Print: 2025-05-26

© 2025 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. A recent update on childhood obesity: aetiology, treatment and complications
  4. Original Articles
  5. Chronotype, sleep, and glycemic control in children and adolescents with type 1 diabetes: a case-control study
  6. Determinants of childhood and adolescent obesity and it’s effect on metabolism in South Indian population
  7. Evaluation of continuous glucose monitoring and nutritional status in glycogen storage diseases
  8. Retrospective assessment of hepatic involvement in patients with inherited metabolic disorders: nine-year single-center experience
  9. Relationships among biological sex, body composition, and bone mineral density in young persons with and without diabetes
  10. The clinical characteristics of 10 cases and adult height of six cases of rare familial male-limited precocious puberty
  11. Optimal timing of repeat thyroid fine-needle aspiration biopsy
  12. Medium-chain acyl-CoA dehydrogenase deficiency in North Macedonia – ten years experience
  13. The effect of antenatal steroids on metabolic bone disease of prematurity
  14. Prader-Willi syndrome gene expression profiling of obese and non-obese patients reveals transcriptional changes in CLEC4D and ANXA3
  15. Early-onset growth hormone treatment in Prader–Willi syndrome attenuates transition to severe obesity
  16. Case Reports
  17. Neonatal severe hyperparathyroidism with inactivating calcium sensing receptor (CaSR) mutation (p.I81K)
  18. Clinical manifestations and molecular genetics of seven patients with Niemann–Pick type-C: a case series with a novel variant
  19. Expanding the genotypic spectrum of 3β-hydroxy-δ5-C27-steroid dehydrogenase (HSD3B7) deficiency: novel mutations and clinical outcomes
https://doi.org/10.1515/jpem-2024-0537
Keywords for this article
ACADM mutations; fatty acid oxidation disorder; medium-chain acyl-CoA dehydrogenase deficiency; neonatal screening

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. A recent update on childhood obesity: aetiology, treatment and complications
  4. Original Articles
  5. Chronotype, sleep, and glycemic control in children and adolescents with type 1 diabetes: a case-control study
  6. Determinants of childhood and adolescent obesity and it’s effect on metabolism in South Indian population
  7. Evaluation of continuous glucose monitoring and nutritional status in glycogen storage diseases
  8. Retrospective assessment of hepatic involvement in patients with inherited metabolic disorders: nine-year single-center experience
  9. Relationships among biological sex, body composition, and bone mineral density in young persons with and without diabetes
  10. The clinical characteristics of 10 cases and adult height of six cases of rare familial male-limited precocious puberty
  11. Optimal timing of repeat thyroid fine-needle aspiration biopsy
  12. Medium-chain acyl-CoA dehydrogenase deficiency in North Macedonia – ten years experience
  13. The effect of antenatal steroids on metabolic bone disease of prematurity
  14. Prader-Willi syndrome gene expression profiling of obese and non-obese patients reveals transcriptional changes in CLEC4D and ANXA3
  15. Early-onset growth hormone treatment in Prader–Willi syndrome attenuates transition to severe obesity
  16. Case Reports
  17. Neonatal severe hyperparathyroidism with inactivating calcium sensing receptor (CaSR) mutation (p.I81K)
  18. Clinical manifestations and molecular genetics of seven patients with Niemann–Pick type-C: a case series with a novel variant
  19. Expanding the genotypic spectrum of 3β-hydroxy-δ5-C27-steroid dehydrogenase (HSD3B7) deficiency: novel mutations and clinical outcomes
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