Two siblings, of a consanguineous family, were referred due to thrombocytopenia (in the range of 30 × 10³ to 80 × 10³/μL), recurrent infections, and hepatosplenomegaly with a working diagnosis of atypical autoimmune lymphoproliferative syndrome (ALPS). The workup revealed elevated levels of vitamin B₁₂, soluble-FAS ligand, and interleukin-10; immunoglobulin G levels and CD4⁻/CD8⁻ double-negative T-cell counts were normal. Bone marrow biopsy revealed reticular fibrosis grade II-III. In the blood smear, large and pale platelets were observed, compatible with the diagnosis of gray platelet syndrome (GPS) (panels A-C; arrows, abnormal platelets; original magnification ×50 [A] and ×100 [B-C]; May-Grünwald Giemsa stain). Targeted next-generation sequencing for genes related to thrombocytopenia revealed homozygosity for a splice-site variation, c.7225-1G>C, in the NBEAL2 gene, causing GPS. Sanger sequencing confirmed this finding in both siblings; both parents were found heterozygous for the mutation.

GPS is an autosomal recessive disorder, caused by defects in the α-granules and characterized by large and pale platelets. Patients with GPS present with bleeding diathesis and a tendency to develop myelofibrosis that can also cause splenomegaly. A previous report included 6 patients initially suspected to have ALPS who were eventually diagnosed with GPS. It is unclear how the platelet granule defects cause elevated cytokine levels. We conclude that a blood smear should be examined for every patient suspected of having ALPS or atypical ALPS to rule out GPS.