syndrome type II Lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak

Abstract Griscelli syndrome (GS) was diagnosed in a 2-year old patient with oculocutaneous albinism and immunodeficiency, but sequencing of RAB27a only revealed a heterozygous mutation. Due to impaired NK and T cell cytotoxicity implying a high risk of developing hemophagocytic lymphohistiocytosis (HLH), he was prepared for hematopoetic stem cell transplantation (HSCT). Unexpectedly, a severe bleeding episode occurred that led to the demonstration of disturbed platelet aggregation, reduced platelet dense granules and impaired platelet degranulation. In combination with neutropenia, this suggested the diagnosis of Hermansky-Pudlak syndrome Type II (HPSII) and a novel homozygous mutation in AP3B1 was detected. None of the three reported HPSII patients had developed HLH and our patient seroconverted to EBV without clinical symptoms. HSCT was therefore withheld, G-CSF therapy was initiated and prevented further bacterial infections. At three years of age, however, the patient developed fulminant HLH without an obvious trigger that was resistant to therapy. This patient shows that careful clinical and molecular diagnosis is essential to differentiate the complex disorders of lysosomal trafficking. HPSII belongs to the group of familial hemophagocytic syndromes and may represent an indication for HSCT. From bloodjournal.hematologylibrary.org by guest on June 5, 2013. For personal use only.