TRMT10A-Related Neurodevelopmental Disorder Without Metabolic Findings

TRMT10A is a tRNA methyltransferase gene associated with a rare autosomal recessive disorder characterized by microcephaly, intellectual disability, epilepsy, short stature, and abnormalities in glucose metabolism. Although an increasing number of patients have been reported, the extent of phenotypic variability and genotype-phenotype correlations remains incompletely understood. We report a 15-year-old male presenting with microcephaly, intellectual disability, epilepsy, and short stature, without evidence of diabetes or other metabolic abnormalities at the time of evaluation. Neurodevelopmental delay was evident from early childhood, and electroencephalography revealed generalized epileptiform activity requiring treatment, whereas brain magnetic resonance imaging was normal. Exome sequencing identified a homozygous stop-gained pathogenic (PVS1, PM2, and PM3) variant in TRMT10A (c.127C>T; p.Arg43Ter), which was confirmed by Sanger sequencing and showed segregation consistent with autosomal recessive inheritance. This case represents one of the rare reported TRMT10A-related syndrome patients in whom diabetes has not yet been documented. This observation highlights the clinical importance of establishing the diagnosis prior to the onset of diabetes, enabling anticipatory monitoring and timely intervention for potential metabolic complications. These findings underscore the importance of considering TRMT10A in the differential diagnosis of patients with microcephaly, intellectual disability, epilepsy, and growth abnormalities, and emphasize the need for longitudinal follow-up to monitor for the possible later development of endocrine and metabolic manifestations.