Objective: Clinically, RAS-associated autoimmune lymphoproliferative disorder (RALD) is characterized by splenomegaly, peripheral lymphadenopathy and autoimmunity. The autoimmune phenotype can present in childhood or adulthood and primarily includes autoimmune hemolytic anemia, immune thrombocytopenia (ITP) and neutropenia. In this report, we present a patient with RALD. The patient showed somatic mutation for NRAS mutation.
Case report: A two-year-old boy was referred with the complaints of ecchymoses. There was no consanguinity between parents and he had a healthy sibling. It was learned that the patient presented with bruises at the age of 12 months, and was follow up with thrombocytopenia, which responded partially and transiently to intravenous immunglobin (IVIG) and steroids. Physical examination at admission revealed hepatosplenomegaly and cervical lymphadenopathies. Complete blood count showed hemoglobin (Hb) 10.6g/dL, mean corpuscular volume (MCV) 74fL, white blood count 11.3×109/L and platelet 15×109/L with monocytosis on blood film. Bone marrow of the patient showed megaloblastic changes and no increase in megakaryocytes. Additionaly, patient was found to have hypergamaglobulinemia. Double-negative (CD4-CD8-) T cells were 2% and a decrease in lymphocyte activation was observed with T and B cell subgroups. Mycophenolate mofetil was started. The patient was followed up with the autoimmune lymphoroliferative syndrome (ALPS) phenotype and genetic work-up revealed NRAS c.38G>A heterozygous mutation. The patient was diagnosed with ALPS type 4 (NRAS somatic mutation). Thrombocytopenia responded to mycophenolate mofetil.
Results: Genetic analysis of the RAS mutation should be performed in cases that does not meet the defined diagnostic criteria of ALPS or JMML.
Conclusion: RAS-related lymphoproliferative disease is a rare genetic disorder of the immune system and is a newly classified disease. RALD presents with autoimmunity, lymphadenopathy, and/or splenomegaly, but without a defect in FAS-dependent apoptosis or an increase in peripheral double negative T lymphocytes. The absolute or relative monocytosis in particular is an important characteristic of this disorder and help differentiate it from ALPS. JMML may be characterized with autoimmunity and may be similar to RALD as a clinical and laboratory phenotype. Approximately 15–30% of patients diagnosed with JMML have somatic, activating RAS mutations. Response to steroids/IVIG in our patient prompted RALD diagnosis, rather than JMML. Finally genetic analysis of the RAS mutation should be performed in cases that does not meet the defined diagnostic criteria of ALPS or JMML.
