Published online Oct 16, 2022. doi: 10.12998/wjcc.v10.i29.10735
Peer-review started: May 27, 2022
First decision: July 12, 2022
Revised: August 10, 2022
Accepted: September 8, 2022
Article in press: September 8, 2022
Published online: October 16, 2022
Dedicator of cytokinesis 8 (DOCK 8) deficiency, also known as autosomal recessive hyper immunoglobulin E (IgE) syndrome, is a combined immunodeficiency disease that was first recognized in 2009. It is caused by genetic alterations (mutations or deletions) in the DOCK 8 gene and is characterized by multiple allergies, elevated IgE levels, and susceptibility to viral and bacterial infections. Early diagnosis is critical to optimize the success of stem cell transplantation.
This study reports the case of a pediatric patient with DOCK 8 deficiency who had negative genetic testing using multiplex primary immunodeficiency (PID) panel and whole-exome sequencing (WES) with a next-generation sequencing method. He presented with chronic diarrhea and was managed as celiac disease based on previous negative workup for immunodeficiency and duodenal biopsy. He developed a generalized vesicular rash which was thought to be dermatitis herpetiformis associated with celiac disease. However, it turned out to be Eczema herpeticum based on positive herpes simplex virus from blood and lesions. The diagnosis was re-evaluated after the child was found to have multiple viral, bacterial, and parasitic co-infections (herpes simplex virus, cytomegalovirus, Epstein-Barr virus, Salmonella, and cryptosporidiosis). Re-evaluation with target gene testing with copy number variation (CNV) analysis and Multiplex Ligation Probe Amplification (MLPA) showed a large homozygous deletion in the DOCK 8 gene, confirming the diagnosis of DOCK 8 deficiency.
Targeted gene testing with CNV analysis might detect deletions that can be missed by WES for diagnosing patients with PID.
Core Tip: Diagnosis of primary immunodeficiency syndromes is challenging, especially those involving the innate immune system. Whole-exome sequencing (WES) is a promising method for diagnosis but has limitations. This article reports a case of delayed diagnosis of Dedicator of cytokinesis 8 deficiency based on negative WES results and highlights the importance of specific gene testing, when the clinical features are suggestive of specific disease, rather than depending on WES alone.