Genetic Characteristics, Infectious, and Noninfectious Manifestations of 32 Patients with Chronic Granulomatous Disease

Abstract

Background:Chronic granulomatous disease (CGD) is a rare genetic disorder characterized by failure of phagocytic leukocytes to destroy certain microbes. We present a study on CGD patients enrolled at a single medical center concerning the infectious and noninfectious complications and genetic properties of the disease.Methods:Icotinamide adenine dinucleotide phosphate oxidase activity and the expression of flavocytochromeb(558) were measured by flow cytometry, and clinical outcomes of the patients were listed in relation to the genetic results.Results:The clinical and genetic findings of 32 pediatric cases with CGD from 23 families were enrolled. Pneumonia and anemia were the most common infectious and noninfectious symptoms. Genetic analysis showed that 10 families (43.5%) carriedCYBBvariants and 13 families (56.5%) have autosomal recessive (AR) CGD, in which 6 families (26%) carriedNCF1variants, 4 (17.4%) carriedCYBAvariants, and 3 (13%) carriedNCF2variants. The median age of clinical onset was 3.3 and 48 months for patients with X-linked CGD (X-CGD) and AR-CGD, respectively. The onset of symptoms before age 1 year was 94% in X-CGD, 28.5% in AR-CGD, and 12.5% in patients with oxidase residual activity. Moreover, a de novo germline mutation at c.1415delG inCYBB(OMIM#300481) and a novel c.251_263del13bp inCYBA(OMIM#608508) were also investigated.Conclusions:Ihydrorhodamine-1,2,3 assay could not detect carrier mother in de novo case withCYBBvariant. Most X-CGD patients have the onset of symptoms before age 1 year. Additionally, residual oxidase activity in AR-CGD causes a delay in onset, diagnosis, and prophylaxis. The protective role of residual activity is limited while the infection is ongoing and becoming serious.