Chronic granulomatous disease. Diagnosis by the dihydrorhodamine assay

Abstract

Chronic granulomatous disease (CGD) is characterized by an alteration of the neutrophil oxidative function. Its inheritance patterns are linked to the X chromosome (X-linked CGD) and autosomal recessive (AR CGD). The dihydrorhodamine (DHR) assay is used for the diagnosis and detection of carriers and provides information on inheritance patterns. Objective: To detect CGD cases in children with recurrent infections and to evaluate their female relatives through the DHR assay to identify carriers and obtain information about possible inheritance patterns. Patients and Method: 107 patients (< 18 years of age) with clinical suspicion of CGD such as pneumonia, lymphadenopathies, and abscesses were included, referred by physicians from public hospitals between 2014 and 2017. Six female relatives of children with CGD were also included. The DHR assay was performed on all patient samples and the results were expressed as neutrophils stimulation index (SI). Results: The median age of patients was 3 years and 62/107 of them were male. The average SI was 39.7 ± 13.8 and a complete shift of DHR was found in 101/107 children. In 2/107 children, no DHR shift was observed (SI = 1.0) indicating possible X-linked CGD, and a third child showed a slight DHR shift (SI = 4.8) compatible with AR CGD. 5/6 female relatives presented a bimodal pattern, showing a carrier status. Conclusions: Three cases of CGD and five female carriers were detected through the DHR assay, being the first time that this technique was used in Paraguay. Information on the most likely inheritance patterns, two X-linked CGD, and one AR CGD case was also obtained.