Gray platelet syndrome
Rare congenital bleeding disorder with gray, agranular platelets.
Gray platelet syndrome (GPS), also known as platelet alpha-granule deficiency, is a rare congenital autosomal recessive bleeding disorder. It is characterized by a reduction or absence of alpha-granules in blood platelets, leading to the release of proteins into the bone marrow and causing myelofibrosis. The condition derives its name from the gray appearance of platelets with a paucity of granules observed on blood films from a patient with a lifelong bleeding disorder.
- Inheritance
- Autosomal recessive
Lore & Background
Gray platelet syndrome typically presents at birth or in childhood with signs such as thrombocytopenia, bruising susceptibility, and epistaxis. The low platelet count is often progressive and can lead to fatal hemorrhages later in life. Affected females may experience irregular menstrual cycles and heavy menstrual bleeding. Myelofibrosis, the buildup of scar tissue in the bone marrow, is a common effect, causing the marrow to produce insufficient blood cells; other organs like the spleen may compensate, leading to splenomegaly.
Reader's Guide
The syndrome is primarily inherited in an autosomal recessive manner, with mutations in the NBEAL2 gene located at 3p21.31. This gene encodes a protein containing a BEACH domain involved in vesicular trafficking, and its expression is required for the development of platelet alpha-granules and thrombocytes in zebrafish. A study of 14 families with GPS found clear autosomal recessive inheritance in 11 families, evidenced by consanguinity or multiple affected siblings with unaffected parents; families included Bedouin, Turkish, Mennonite, French, German, Somali, African American, and mixed Northern and Southern European backgrounds. In Japan, 24 affected patients in a single family showed at least one instance of male-to-male transmission, consistent with autosomal dominant inheritance. Diagnosis requires demonstration of absent or reduced alpha-granules by electron microscopy, and high serum vitamin B12 levels are common. There is no specific treatment, but management includes desmopressin and, for those with platelet counts dropping to approximately 30,000/microliter, splenectomy. Prognosis is generally good early in life when thrombocytopenia is mild.
Did You Know?
- The name 'gray platelet syndrome' comes from the gray appearance of platelets with a paucity of granules on blood films.
- Only about 60 cases of Gray platelet syndrome have been recorded worldwide.
- The NBEAL2 gene mutation causing GPS is located on chromosome 3p21.31.
More in Genetic disorders with OMIM but no gene 1-24
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