P141 Mirage syndrome with bone marrow stem cell transplant: A case report

Abstract

MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes and enteropathy) syndrome is a recently described multisystem disorder that is related to gain of function of the growth repressor SAMD9. Due to the dominant suppressive effect of SAMD9 mutants, MIRAGE syndrome is associated with high mortality. A new publication this year suggests bone marrow transplantation (BMT) may be necessary for survival. Here we report a case of a patient who developed unexpected post-transplant complication and raise concerns of BMT as a treatment for the MIRAGE syndrome patients. A 23-month female with a history of congenital amegakaryocytic thrombocytopenia appears associated with MIRAGE syndrome, received a 9/10 matched (one mismatch at C locus) unrelated donor peripheral stem cell transplant in April of 2016. Although the patient has fully engrafted, her graft did not function properly. She had hemolytic anemia, marked decreased granulopoiesis in the marrow and persistent neutropenia, which further resulted in several episodes of sepsis. The underneath etiology is likely autoimmune related reactivity. Further tests excluded HLA antibody mediated response. Instead an alloreactive clonal T cell population was found in her bone marrow, which was consistent with the clinical observation that her neutrophil counts were improved to normal level after the T-cell-targeted chemotherapy. However, the patient passed away 10 months post-transplant due to respiratory failure. The patient was identified to have features of thymic hypoplasia, atrophic ovaries and bilateral adrenal hypoplasia that is consistent with the MIRAGE syndrome diagnosis. Moreover, the histology of the patient’s hypoplasia thymus showed lymphocyte depletion, lacking of corticomedullary demarcation, absence of Hassall’s corpuscles and extensive adipocytic infiltration. These results suggest the patient’s thymus is defective in supporting T cell development, and the development of the alloreactive T cells that targeted specifically her neutrophil is most likely due to a disfunction of her thymus. Since thymic hypoplasia is one of the features of MIGRAGE syndrome, this case suggests bone marrow transplant might not be the primary choice of the treatment for MIRAGE syndrome patient.