Recurrent and unusual infections unmasking a rare inborn error of immunity: a case report RAS-associated Autoimmune...

RAS-associated Autoimmune Lymphoproliferative Disease (RALD) is a rare, non-malignant lymphoproliferative disorder caused by somatic mutations in RAS genes that impair lymphocyte apoptosis. Patients often present with features of lymphoproliferation, autoimmune manifestations, and an increased risk of malignant transformation.

We report the case of a 3-year-old boy with splenic microabscesses and Burkholderia pseudomallei IgM serology positivity, who was treated as melioidosis. He had recurrent respiratory infections and chronic rhinorrhoea since the age of one year. Clinical examination revealed persistent lymphadenopathy and hepatosplenomegaly. Laboratory investigations demonstrated persistent absolute monocytosis and thrombocytopenia, while immunological evaluation showed elevated IgM levels and B-cell lymphocytosis. Whole exome sequencing identified a heterozygous pathogenic variant in NRAS, NM_002524.5:c.35G > C, NP_002515.1:p.Gly12Ala, establishing the diagnosis of RALD. The patient was subsequently started on antibiotic prophylaxis and immunoglobulin replacement therapy, and his family was counseled regarding the potential role of immunosuppressive therapy and hematopoietic stem cell transplantation (HSCT) in future management.

This case highlights the coexistence of an unusual infection with a rare inborn error of immunity, expanding the recognized infectious spectrum of RALD. It underscores the importance of considering RALD in patients presenting with recurrent or atypical infections and persistent lymphoproliferative features. Early recognition and molecular genetic testing are essential for confirming the diagnosis and guiding individualized management.