Autism spectrum disorder in the Republic of Moldova: epidemiology, genetic markers, and serum free copper as a metabolic biomarker

Abstract

Abstract Background. Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with rising global prevalence, currently estimated at 1–2% worldwide. Despite this, epidemiological data and from the Republic of Moldova remain scarce, and access to genetic counseling and biomarker-based diagnostics is limited. Methods. This study integrates (1) epidemiological data from the Republic of Moldova, including 2024 Census estimates and 2023–2026 genetic counseling records; (2) genetic screening results from the Laboratory of Human Molecular Genetics at the Institute of Mother and Child; and (3) serum free copper (non-ceruloplasmin-bound copper, NCC) measurements in a cohort of 27 children with ASD from Moldova. Results. With an estimated population of ~2,423,000, between 24,000 and 48,000 individuals may be living with ASD in Moldova. Based on an estimated pediatric population of ~484,600 (20% of Moldova's total population of ~2,423,000) and an ASD prevalence of 1.5%, the expected number of children with ASD in Moldova is approximately 7,269. Of these, only 292 children (4.02%) accessed genetic counseling services between January 2023 and June 2026, revealing a substantial gap between estimated needs and actual service provision. Genetic testing identified pathogenic mutations in MECP2 (42% of suspected Rett syndrome cases), an insertion in RELN gene (c.6_1 dup, rs55656324), dup 27 exon in TRPM1 gene and multiple chromosomal abnormalities including 22q11 duplication syndrome, Phelan-McDermid syndrome, Prader-Willi syndrome, and others. Serum NCC levels in the ASD cohort were markedly elevated: mean 34.06 μg/dL, median 35.88 μg/dL - more than double the accepted upper normal limit of 15 μg/dL. Notably, 95% of children exceeded this threshold, and 90% had values above 25 μg/dL. Conclusions. ASD prevalence in Moldova is likely underestimated, with a substantial diagnostic gap. Genetic testing reveals a significant yield of pathogenic variants. Serum free copper (NCC) is consistently elevated in Moldovan children with ASD and represents a promising, accessible biomarker for early screening. Larger prospective studies and a national ASD registry are urgently needed.