Friday, March 24, 2017
Grand Ballroom II/III (The Westin Seattle)
Jay P. Patel, MD (Seattle Children's Hospital)
MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) is a newly described syndrome in patients with heterozygous mutations of SAMD9. Immunodeficiency in these patients has not been well described. We report a 15 month old male with a history of failure to thrive, adrenal insufficiency and severe respiratory viral infections requiring intubation two times in the pediatric intensive care unit. Sequencing of SAMD9 showed a heterozygous missense mutation. SAMD9 has been described to play a role in the innate immune response and defense against viral pathogens. Exome sequencing also showed a variant of unknown significance in WAS, but WASp protein expression in peripheral blood lymphocytes was normal. Bone marrow evaluation revealed myelodysplasia with the cytogenetic finding of monosomy 7. His immune evaluation was significant for hypogammaglobinemia (IgG: 190 mg/dL), B-lymphopenia (101/mm3), CD4 T-cell lymphopenia (625/mm3) with an inverted CD4:CD8 ratio of 0.7. Phenotyping showed highly immature CD4 and CD8 T-cell lineages and absent immature CD19 B cells with significant B-lymphopenia. IVIG was started for hypogammaglobinemia. The findings in this patient suggest that SAMD9 plays a role in immune cell development and function. Immune evaluation in additional MIRAGE patients would be informative.