Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency is a rare autosomal recessive primary immunodeficiency characterized by immune dysregulation and clinical heterogeneity. Diagnostic delay is frequent and contributes to significant morbidity. We report five pediatric cases managed at the Pediatric Hematology Department of the National Bone Marrow Transplantation Center in Tunis.
Clinical, immunological, and genetic data of five pediatric patients with LRBA deficiency were retrospectively reviewed.
Five patients (three females, two males), all but one from consanguineous families, were included. Mean age at symptom onset was 90 months, with a mean diagnostic delay of 38 months (mean age at diagnosis, 128 months). Evans syndrome was present in all patients, being the inaugural manifestation in three. Autoimmune enteropathy with chronic diarrhea occurred in two patients and autoimmune hepatitis with primary biliary cholangitis in one. Recurrent infections were observed in two patients; no lymphoproliferation was noted. Immunological work-up showed hypogammaglobulinemia in three patients; lymphocyte subsets were normal in all. Molecular analysis identified homozygous class 4 or 5 LRBA variants in all cases. Three patients received immunoglobulin replacement therapy. All were treated with systemic corticosteroids (mean 45 months) and mycophenolate mofetil (mean 41 months); azathioprine and sirolimus were used in one patient each. One patient underwent hematopoietic stem cell transplantation. Sustained remission of Evans syndrome was not achieved in any patient. Two patients died from severe hemorrhagic complications, including one post-transplantation.
This series underscores the clinical heterogeneity of LRBA deficiency and the challenges of managing severe autoimmune manifestations. Care remains difficult in settings without access to targeted therapies.
