Emerging spectrum of DOCK8 deficiency in children and challenges associated with providing treatment: experience from a tertiary referral centre in India

Abstract

Abstract The study describes the course of children with DOCK8 deficiency, their stormy clinical course, discrete infection pattern, and challenges during the treatment. The retrospective study included children up to 18 years of age diagnosed to have genetically proven DOCK8 deficiency from January 2013 to January 2023. A total of nine children were included, with a median age of five years. Clinical presentations included eczema (2/9), viral infections (4/9), recurrent sinopulmonary infections (3/9), impetigo (2/9), autoimmune hemolytic anemia (1/9) and Epstein-Barr virus driven malignancy (1/9). Other infections noted were molluscum contagiosum in two children, cytomegalovirus colitis in one child, and recurrent Klebsiella pneumoniae meningitis. The outcomes of hematopoietic stem cell transplantation (HSCT) remained poor (n=5, three haploidentical HSCT, one each matched family and unrelated donor HSCT), due to early and refractory viral reactivation, with 17,00,000 copies of cytomegalovirus in one child and 8,53,95,600 copies of adenovirus in another child. Secondary late graft failure was noted in one child, two years following a matched sibling donor HSCT. The one who underwent a matched unrelated donor HSCT was doing well and was infection free. The clinical course without HSCT had been stormy, as seen in a child with Burkitt's lymphoma, who succumbed to refractory cytomegaloviral meningoencephalitis despite being in remission following chemotherapy. DOCK8 deficiency patients are included in the Hyper IgE syndrome spectrum. HSCT poses significant challenges in these children with refractory viral infections. Collaborative work and research are required to decide the optimal care for these children to guide better treatment outcomes.