Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition with heterogeneous genetic underpinnings, and congenital disorders of glycosylation (CDGs) represent an emerging etiological subgroup.Case Presentation: This case report details a 14-year-old male boy from a consanguineous family with an unremarkable birth history presenting with dysmorphic features, nonverbal autism spectrum disorder (ASD), global developmental delay (GDD), and abrupt school avoidance, harboring a novel homozygous STT3B variant (NM_178862.5:c.1089 T>G; p.Ser363Arg).His growth trajectory has remained significantly below average, with a current height of 127 cm (–4.2 SD) and poor growth velocity (4 cm/year). Pubertal assessment showed early signs (Tanner stage 2), with LH and testosterone levels trending upward. Bone age (12.8 years) with 2 SD was delayed, and IGF-1 was markedly low (19 ng/mL). GH stimulation testing could not be performed due to hypotension.Then the decision was made to initiate a trial of recombinant growth hormone (rGH) therapy, given the significant height deficit, delayed bone age, and clinical signs suggestive of evolving puberty. The patient's sister was trained to administer daily GH injections (1.2 mg), and the family provided informed consent after thorough counseling. This is his growth chart [Figure 1].Discussion: STT3B encodes a critical subunit of the oligosaccharyltransferase complex, and pathogenic variants are linked to CDG type 2. Whole-exome sequencing identified the c.1089 T>G variant (rs786205946) with a minor allele frequency of 0.00003 (gnomAD v2.1.1), classified as a variant of uncertain significance (VUS) per ACMG/AMP criteria (PM2, PP3).Computational analysis yielded a CADD score of 28.3, suggesting a deleterious impact. Clinical evaluation revealed profound speech regression (loss of verbal communication at age 3 years), intellectual disability, short stature (< 1st percentile), delayed puberty (testicular volume 2 mL, Tanner I), and dysmorphic features (frontal bossing, broad nasal tip). Behavioral comorbidities included school refusal, anxiety, and nonverbal communication reliance (pointing, PECS). Neuroimaging and metabolic screening were unremarkable.Management emphasized multidisciplinary coordination: speech therapy with the Picture Exchange Communication System (PECS), growth hormone initiation counseling, and school accommodations for anxiety-driven avoidance.Conclusion: This case expands the phenotypic spectrum of STT3B-related disorders, previously associated with hepatic and skeletal manifestations, by linking the gene to ASD regression and adolescent behavioral challenges.It highlights the critical role of genetic testing in consanguineous populations with atypical ASD trajectories and underscores the need for proactive management of puberty delays in neurogenetic CDGs. Further functional studies are warranted to elucidate the mechanistic role of STT3B in neurodevelopment.
