Gray platelet syndrome (GPS) is a rare inherited platelet disorder caused by defective α-granule biogenesis. Emerging evidence suggests that GPS represents a multisystem disorder with immune and inflammatory manifestations. We report three siblings from a single family with genetically confirmed GPS who presented with lifelong thrombocytopenia and mild to severe bleeding symptoms. Notably, all affected individuals had persistently elevated serum vitamin B12 of unclear etiology. One sibling had concomitant type 1 diabetes mellitus and biopsy confirmed celiac disease. This familial case series highlights the phenotypic heterogeneity of GPS and supports its recognition as a multisystem disorder. The consistent finding of hypercobalaminemia represents a notable but poorly understood feature, while the coexistence of autoimmune disease suggests underlying immune dysregulation related to NBEAL2 deficiency. Gray platelet syndrome may involve metabolic and autoimmune manifestations beyond bleeding. Awareness of these associations is essential for comprehensive evaluation and long-term management of affected patients.
Alzeerelhouseini et al. (Tue,) studied this question.