PB1295 - Dose Genotype Correlate with Phenotype Among Glanzmann Thrombasthenia Patients?

Background: Glanzmann thrombasthenia (GT) is a rare bleeding disorder, with an incidence of 1:1,000,000. However, in Madinah, Saudi Arabia, GT prevalence was 1:10,000.

Aims: Phenotype comparison of three mutations carried by 83 GT patients.

Methods: This is a report from the AlMadinah GT registry. Disease severity is defined based on clinical severity, where severe is defined as bleeding continued for more than 3 days, a drop in hemoglobin for >2 grams / L, or needing admission to the ICU. Moderate is defined as bleeding that needs hospital admission, while mild is bleeding that can be stopped at home.

Results: 125 GT patients were studied: 67 (54%) females and 58 (46%) males. The median age was 16.5. 98% of GT patients were the product of consanguineous marriage. Family history of GT was reported in 107 (86%) cases. 18 mutations have been identified: 15 mutations in the ITGA2B gene and 3 mutations in the ITGB3 gene. 42 GT patients carry the mutation ITGA2B:exon20:c.1879-2A>G (Mutation 1). 28 GT patients carry the mutation ITGB3:exon13:c.2112delC (Mutation 2). 13 GT patients carry the mutation ITGA2B:exon13:c.1210+5G>A (Mutation 3). Table 1 shows the comparison of disease course and bleeding frequency among the 3 different mutations. The P-value of the clinical course was 0.00001 when comparing mutations 2 and 1 and 0.03 when comparing mutations 2 and 3 but was 0.6 when comparing mutations 1 and 3. The P-value of the bleeding frequency was < 0.0000001 when comparing mutation 2 and 1 and 0.03 in comparing mutation 2 to 3 but was 0.003 when comparing mutation 1 to 3.

Conclusion(s): Genotype can affect the phenotype in GT patients, where the mutation ITGB3:exon13:c.2112delC (Mutation 2) has a more severe disease course and more frequent bleeding.