Type 2 Diabetes in a Portuguese Adolescent With Hijazi-Reis Syndrome

Hijazi-Reis syndrome is a recently described, rare, X-linked neurodevelopmental disorder caused by loss-of-function variants in the TCEAL1 gene. Fewer than 15 cases have been reported to date, with key features including developmental delay, especially affecting expressive speech, intellectual disability, autistic traits, and variable systemic findings. We describe the case of a Portuguese girl with severe intellectual disability, absent speech, autistic traits, obesity, and mild dysmorphic facial features. Genetic testing identified a de novo exon 3 deletion in TCEAL1, confirming the diagnosis of Hijazi-Reis syndrome. At age 14, she developed type 2 diabetes with preserved insulin secretion and negative autoimmune markers. This first Portuguese case adds to the limited clinical descriptions of Hijazi-Reis syndrome and documents the occurrence of type 2 diabetes in an affected adolescent. As further cases are reported, consideration of metabolic aspects may support comprehensive follow-up and multidisciplinary care in affected individuals.