PB1303 - Identification of a novel mutation in the NBEAL2 gene in a patient with gray platelet syndrome

Background: Gray platelet syndrome (GPS) is an inherited bleeding disorder with platelet granule abnormality known as storage pool disease. Blood smear in patient with GPS exhibit large grayish platelets with reduced staining affinity, attributed to the deficiency of platelet α-granules and their contents. GPS is an extremely rare disease, with fewer than 100 pedigrees reported worldwide to date. The genetic basis of GPS includes mutations in the NBEAL2 (Neurobeachilin-like 2) gene, first reported in 2011 for autosomal recessive cases, and in the GFI1B (growth factor independent 1B) gene, reported in 2014 for autosomal dominant cases.

Aims: We present a case of GPS with a novel mutation in the NBEAL2 gene.

Methods: A 40-year-old female with a medical history of iron deficiency anemia presented to her primary care physician with purpura on her extremities. Although her blood tests indicated a platelet count, prothrombin time (PT), and activated partial thromboplastin time (APTT) were within normal range, hemostatic function tests, revealing prolonged hemostasis time, led to her referral to our department on suspicion of platelet dysfunction.

Results: Her blood tests revealed a platelet count of 138x10^9/L, and May-Giemsa staining of blood smear showed characteristic gray platelets. Electron microscopy revealed α-granules with vacuolar structures. Platelet aggregation tests demonstrated abnormal responses, with ADP (10μM) at 73%, collagen (3μg/mL) at 9%, epinephrine (10μM) at 12%, and ristocetin (1.5mg/mL) at 90%. Whole-genome sequencing identified a novel mutation in the NBEAL2 gene (c.1531C>G, p.Arg511Gly). No mutations were detected in the GFI1B gene. She was diagnosed with GPS, and treated with tranexamic acid for minor bleeding. In the case of further bleeding, she is advised to see us for hemostatic treatment.

Conclusion(s): We identified a novel mutation in the NBEAL2 gene in patients with GPS. Further case series are needed to elucidate the relationship between this mutation and GPS.