PB1382 - Inherited platelet function disorder in pediatric patient with identified CalDAG-GEFI deficiency

Background: Inherited platelet disorders (IPDs) are a group of genetically heterogeneous disorders with platelet dysfunction (Inherited platelet function disorders), abnormal counts of platelets (inherited thrombocytopenias) or both that manifest as a cause of excessive mucocutaneus bleeding.
Among the signal transduction pathways is the calcium and diacylglycerol (DAG)-regulated guanine exchange factor-1 (CalDAG-GEFI) deficiency (OMIM®615888). The function of the fibrinogen receptor integrin αIIbβ3 is affected in the mutation of RAS guanyl-releasing protein-2 gene (RASGRP2) that encodes for CalDAG-GEFI. The mutation results in impaired platelet aggregation and ADP-induced integrin αIIbβ3 activation defects in humans, known as platelet-type bleeding disorder type 18 (BDPLT18).

Aims: Presentation of a novel pathogenic variant for the RASGRP2 gene and a review of previously reported cases

Methods: We report the case of a 10-year-old Mexican girl who presented with history of gingival bleeding, and at physical examination short stature, horizontal nystagmus, psychomotor retardation. Initial laboratory studies include blood counts, which show reduced hemoglobin levels, normal platelet count, and the white series. Von Willebrand Disease was suspected and ruled out (193.3 % antigenic,112% activity). The Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) were reported normal, although slightly prolonged PT (Table 1). Consequently, levels of Factor V, FVII, FVIII, and FX were requested and reported within normality. Her management consisted of tranexamic acid, and episodic recombinant factor VIIa (rFVIIa) as required, with good control of bleeding.

Results: Platelet aggregometry was requested, exhibiting impaired aggregation response to adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. A sample is taken for a genetic panel that reveals a novel homozygous pathogenic variant for the RASGRP2 gene (Table 2).

Conclusion(s): The use of molecular genetic studies in the final steps of screening can benefit patients with a strong diagnostic suspicion of IPFDs with early diagnostic identification, bleeding prevention, and control of some of the chronic bleeding problems.