Clinical and genetic description of patients with chronic granulomatous disease in a pediatric hospital

Abstract

Introduction: Chronic granulomatous disease is a congenital immune disorder characterized by increased susceptibility to fungal and bacterial infections and dysregulated inflammation. It is caused by defects in the NADPH oxidase and EROS protein.

Objective: To characterize clinically and genetically four patients with chronic granulomatous disease at the Hospital Infantil de México Federico Gómez.

Materials and methods: Patients diagnosed with chronic granulomatous disease by the dihydrorhodamine oxidase technique were molecularly and genetically characterized by measuring NADPH oxidase subunit expression and exome sequencing and analysis. The different clinical variables were obtained from clinical files, and each case was described.

Results: We described four male patients with chronic granulomatous disease: two with pathogenic variants in CYBB, one with CYBB and adjacent genes deleted, and one without p47phox expression. Mothers of the three patients with mutated CYBB were carriers. All three cases with CYBB had severe and recurrent infections in addition to Calmette-Guérin bacillus infection as the initial manifestation. The autosomal recessive case of p47phox deficiency had the mildest clinical presentation. Deleting CYBB and several contiguous genes was associated with a poor prognosis. None of the patients received hematopoietic stem cell transplantation.

Conclusions: Chronic granulomatous disease, secondary to pathogenic variants in CYBB was the most common in these Mexican patients. The carrier mothers should be followed clinically because of the potential risk of inflammatory, autoimmune, and infectious manifestations. One of the first manifestations was Calmette-Guérin bacillus infection, and in countries such as Mexico, where this vaccine is administered, cases with any type of adverse reaction should be evaluated to rule out chronic granulomatous disease.