Protein Kinase Cδ deficiency in Arab children: A link to fatal monogenic lupus and BCGitis susceptibility.

BackgroundMonogenic lupus is a rare form caused by single pathogenic gene variants, leading to diverse clinical symptoms from multi-organ involvement. Variants in Protein Kinase Cδ (PRKCD) are known contributors, though remain underreported.ObjectiveTo describe the phenotypic, genetic, and outcome profiles of Arab children with monogenic lupus and PRKCD deficiency.MethodsWe retrospectively reviewed medical records of children with PRKCD deficiency lupus at two institutions in Saudi Arabia and Oman. The cohort included genetically confirmed and clinically suspected cases (due to unavailable testing in deceased siblings). Demographic, clinical, genetic, and follow-up outcome data were collected and analyzed.ResultsSeven children (four females) from three unrelated consanguineous Arab families were identified, with four having confirmed PRKCD variants. All presented before the age of 2 years with fever and multi-organ involvement. Recurrent infections were common, with three patients developing BCGitis. All had high ANA, ds-DNA, and APL, with variable positivity for other autoantibodies. Complement studies revealed low C3/C4, and reduced C1q and CH50 in four patients. Treatment included corticosteroids and sequential immunosuppressive therapy, with five patients receiving biologic agents. While four achieved low disease activity on intensive treatment, three died due to severe disease and serious infections.ConclusionOur findings demonstrate that PRKCD deficiency is associated with autosomal recessive monogenic lupus, characterized by severe and potentially fatal outcomes. They also confirm the link with BCGitis susceptibility. The observed heterogeneity in disease course and treatment response highlights the need for precision medicine and warrants further investigation.