Clinical and molecular profile of 20 patients with DOCK8 deficiency-a single-center experience from Southern India

DOCK8 deficiency is the most common cause of autosomal recessive hyper-IgE syndrome (AR-HIES). The clinical spectrum is wide resulting in combined immunodeficiency, atopy, autoimmunity, and malignancies. To study the clinical and molecular profile of 20 patients with DOCK8 deficiency. Four hundred and eight patients with various inborn errors of immunity (IEIs) were diagnosed in the Pediatric Immunology Unit of our hospital during the study period of February 2017 to August 2023. Based on the clinical and immunological phenotype, DOCK8 deficiency was suspected in 31 patients. Genetic studies confirmed DOCK8 deficiency in 20 patients, and their profile was analyzed in detail. Twenty patients from 17 kindreds were diagnosed with DOCK8 deficiency. The female-to-male ratio was 1.2:1. The mean age at onset of symptoms and diagnosis was 9.8 and 69.8 months, respectively. Thirteen out of 17 families (76%) reported consanguinity. Eczema was the presenting manifestation in 19 patients (95%). Mucocutaneous manifestations included oromucosal hyperpigmentation (n = 8), scalp seborrhoea (n = 2), psoriasis (n = 2), and alopecia (n = 1). The spectrum of infections included pneumonia (n = 14), otitis media (n = 6), gastrointestinal infections (n = 6), cutaneous viral infections (n = 5), oral candidiasis (n = 4), and meningoencephalitis (n = 2). Three patients had developed bronchiectasis. Four patients had autoimmune manifestations including autoimmune hemolytic anemia (n = 2) and vasculitis (n = 2). The whole exome sequencing showed deletions (8 kindreds) as the most common mutation in the DOCK8 gene. Overall, 11 of these mutations were novel. Ten patients were on monthly intravenous immunoglobulin therapy and antibiotic prophylaxis at the time of writing this paper. Three patients underwent hematopoietic stem cell transplants elsewhere, two of whom succumbed to post-transplant complications and one is doing well. Nine patients died during the study period. We present one of the largest single-center experiences on DOCK8 deficiency from India. A significant delay in the diagnosis contributed to poor outcomes in our cohort.