Clinical and molecular features of LRBA.

Background : Primary immune regulatory disorders (PIRD) is a new term coined for a group of PID where autoimmune complications predominate. Herein we present a case series of 10 cases with lipopolysaccharide (LPS)-responsive and beige-like anchor protein (LRBA) deficiency who presented with multiple autoimmunities. Methods: 10 patients with molecular diagnosis of LRBA deficiency were included and their clinical data was evaluated. Results: The mean age of onset was 4.3 years. Male to female ratio was 7:3. 8/10 had 2 or more autoimmune disease with autoimmune cytopenia being the commonest. Other autoimmune diseases seen were autoimmune hepatitis, inflammatory bowel disease, enteropathy, diabetes melitis, thyroiditis, CNS vasculitis, dermatitis and alopecia areata. All patients had evidence of lymphoproliferation with generalized lymphadenopathy and/or hepatosplenomegaly. 5/10 had hypogammaglobinemia, 3/10 had low T cells, two of whom had CD4 lymphopenia. 4/10 had low B and NK cells. 2 had compound heterozygous and 8 had homozygous mutations in LRBA gene. The treatment was diverse and included corticosteroids, cyclosporine, azathioprine, cyclosporine, rituximab, sirolimus and abatacept. One child has undergone successful HSCT and currently doing well. Conclusion: Patients with LRBA deficiency present with a broad range of clinical manifestations. High index of suspicion for a monogenic cause for polyautoimmunity in early childhood can reduce time delay in diagnosis. With increasing availability of transplant facilities the outcome for these patients can be significantly better.