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Exact prevalence of the disorder is not known. About 60 cases from various populations around the world have been described in the literature to date. It affects males and females equally.

Onset of clinical symptoms is generally in the neonatal period or in early childhood while age of diagnosis is variable. Presenting features include low platelet counts, easy bruising (petechiae), prolonged bleeding and epistaxis. Patients often have myelofibrosis and splenomegaly. Bleeding tendency is usually mild to moderate in GPS patients with mild thrombocytopenia. However, thrombocytopenia and myelofibrosis in GPS are progressive in nature; GPS may result in fatal hemorrhage especially in adulthood when platelet counts are further decreased. Female patients may develop menorrhagia.

GPS is caused by mutations in the NBEAL2 gene. Absence or marked reduction of alpha-granules in platelets underlie the disorder. Alpha-granules are the most abundant vesicles in platelets and store proteins that promote platelet adhesiveness and wound healing when secreted during platelet activation.

Diagnosis is based on clinical findings and requires demonstration of absence or marked reduction of alpha-granules by electron microscopy (EM). Absence of alpha-granules is an isolated finding in GPS; dense bodies and other platelet organelles and polymorphonuclear leukocytes are normal on EM. Peripheral smears show typical large, pale gray platelets. Most patients also have high serum vitamin B12 levels. Bone marrow sampling is not required for diagnosis of GPS, but might be needed to evaluate myelofibrosis occurring in GPS and to exclude other disorders.

Differential diagnosis includes other platelet disorders such as macrothrombocytopenias (Bernard-Soulier syndrome, MYH9-related thrombocytopenia, macrothrombocytopenia with mitral valve insufficiency, Mediterranean macrothrombocytopenia), idiopathic thrombocytopenic purpura (ITP) (see these terms), as well as other disorders with hypogranular or gray platelets such as myelodysplastic syndrome (MDS, see this term), myocardial infarction, other causes of hypersplenism, and congenital conditions such as alpha-delta granule deficiency, white platelet syndrome and Quebec platelet disorder (see these terms). Electron microscopy of platelets differentiates GPS from the autosomal dominant variant and from the X-linked variant described as X-linked thrombocytopenia with thalassemia, caused by mutations in GATA1 gene (see this term). These variants display abnormalities not limited to alpha-granules.

Prenatal diagnosis is possible if the NBEAL2 mutation has been identified in the family.

GPS is inherited in an autosomal recessive manner (autosomal dominant inheritance has been reported in only 1 family). Siblings of an affected patient are at 25 % risk for GPS, while the risk for offspring of a GPS patient is not significantly higher than for the general population.

There is no specific treatment but management involves anticipating and preventing risks of bleeding (e.g. possible platelet transfusions before surgery). Treatment may include administration of desmopressin. Splenectomy should be considered to increase the platelet counts in patients whose platelet counts decrease to approximately 30,000/microliter.

Prognosis is generally good early in life when thrombocytopenia is mild. GPS patients with platelet counts less than 30,000/microliter are at risk for life-threatening bleeding.