Expanding the Phenotype of OTUD6B-Related Disorder: Neurodevelopmental Impairment and Immune Dysregulation with Immune Thrombocytopenic Purpura: A Case Report

Abstract

Background: OTUD6B-related disorder is a rare autosomal recessive condition primarily associated with neurodevelopmental impairment, seizures, and dysmorphic features. Its possible role in immune dysregulation has not been well documented.

Case Presentation: We describe an 11-year-old Palestinian female with a homozygous OTUD6B (c.173-2A>G) mutation who presented with global developmental delay, cavovarus foot deformities, scoliosis, seizures, and recurrent infections. During hospitalization, she developed severe thrombocytopenia (platelet count 8,000/µL) with epistaxis, hematemesis, and a purpuric rash. Laboratory evaluation confirmed immune thrombocytopenic purpura (ITP). She responded to intravenous immunoglobulin (1 g/kg, total dose 18 g), methylprednisolone, and supportive care, with platelet recovery to 17,000/µL within 24 hours. Her younger sister, also carrying the same OTUD6B mutation, exhibited developmental delay and seizures but no hematologic complications.

Discussion: This case suggests a potential novel association between OTUD6B mutations and immune dysfunction, particularly ITP. The observation expands the clinical spectrum of OTUD6B-related disorders beyond neurodevelopmental impairment, raising the possibility of immune dysregulation through disrupted deubiquitination pathways and type I interferon signaling.

Conclusion: Recognition of hematologic manifestations in OTUD6B-related disorder is essential for comprehensive patient management and genetic counseling. Further research is needed to clarify the immunological role of OTUD6B and its contribution to autoimmune conditions.