Clinical and molecular profile of 17 patients with DOCK8 deficiency: A single-centre experience from Southern India

Abstract Introduction 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. Objectives To study the clinical and molecular profile of 17 patients with DOCK8 deficiency. Methods Three hundred sixty 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 April 2023. Based on the clinical and immunological phenotype, DOCK8 deficiency was suspected in 21 patients. Genetic studies confirmed DOCK8 deficiency in 17 patients and their profile was analysed in detail. Results Seventeen patients from 14 kindreds were diagnosed with DOCK8 deficiency. Thirteen of these families (92%) reported consanguinity. Our cohort had eight male and nine females. The mean age at onset of symptoms and diagnosis was seven months and 5.8 years respectively. Eczema was noted in 16 patients. Mucocutaneous manifestations included oromucosal hyperpigmentation(n=6), scalp seborrhoea(n=2), alopecia(n=1) and perianal tag(n=1). The spectrum of infections included pneumonia(n=11), diarrhea (n=5), otitis media (n=4), mucocutaneous candidiasis(n=3),meningoencephalitis(n=2), and cutaneous viral infections (n=3). Two patients had developed bronchiectasis. Autoimmune manifestations were noted in four patients and included autoimmune haemolytic anaemia (n=2) and vasculitis (n=2). Single exonic deletions(n=10) in DOCK8 gene were the most common mutations observed and 13 of these were novel. Twelve patients were on monthly intravenous immunoglobulin therapy 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. Overall, eight patients died during the study period, while nine patients continue to remain on follow-up. Conclusion We present one of the largest single-centre experiences on DOCK8 deficiency from India. A significant delay in the diagnosis contributed to poor outcome in our cohort.