Unmasking chronic granulomatous disease: A routine diagnostic workup in a Brazilian children's hospital.

Abstract

The diagnosis of chronic granulomatous disease (CGD), a congenital immunodeficiency affecting phagocyte function, remains a challenge for patients in Latin America. It is well established that dihydrorhodamine (DHR) flow cytometry is the most commonly used screening assay; however, few pediatric immunology centers in Brazil perform this test. This study reports data from a routine diagnostic workup for CGD conducted at a Brazilian children's hospital. A three-year prospective study was performed, enrolling children with clinical features suggestive of immunodeficiency who were screened using DHR. Sanger sequencing of the NCF1 (neutrophil cytosolic factor 1) and CYBB (cytochrome b-245, beta chain) genes was conducted in children with two consecutive abnormal DHR results. A total of 255 patients-62% males-with a median age of 3.2 years (range: 1 month-17.8 years) were evaluated. Six patients (2.4%) had abnormal DHR tests, and four of them (1.6%) received a definitive diagnosis of CGD. Most children presented with pneumonia and/or abscesses during the first year of life as the clinical manifestation of CGD. Two of the four diagnosed patients were receiving continuous antibiotics and two underwent transplantation. Pathogenic variants were identified in NCF1 (three cases) and CYBB (one case). The hospital-based diagnostic workup for CGD identified approximately one new case per 60 tested patients, indicating a high frequency of the disease in the study population. This approach may represent a valuable strategy for identifying new pediatric CGD cases in resource-limited settings.