First Case of Chronic Granulomatous Disease Due to NCF1 Mutation Successfully Treated with Pioglitazone

Introduction Chronic granulomatous disease (CGD) is a rare genetic disorder resulting from mutations in the genes encoding subunits of the nicotinamide adenine dinucleotide phosphate oxidase complex. This condition leads to life-threatening infections and granuloma formation. Hematopoietic stem cell transplantation (HSCT) is a curative treatment for CGD but is complicated by the availability of matched donors and active infections. Recent studies suggest that pioglitazone, a peroxisome proliferator–activated receptor gamma agonist, may offer therapeutic potential in CGD. This report presents the first documented case of CGD due to an NCF1 mutation, treated successfully with pioglitazone. Case Presentation The patient is a 4-year-old girl from a non-consanguineous family with a history of recurrent infections, including necrotizing pneumonia, lymphadenitis, and sepsis, requiring multiple hospitalizations and broad-spectrum antibiotics. Despite multiple treatments, including anti-tuberculosis therapy, her condition persisted. A CT scan revealed poly-necrotizing pneumonia. Although laboratory findings, including complete blood count, immunoglobulin levels, and T cell markers, were normal, CGD was confirmed by a dihydrorhodamine (DHR) test showing absent right shift upon PMA stimulation. Whole exome sequencing (WES) failed to identify mutations due to NCF1 being a pseudogene. However, PCR–restriction fragment length polymorphism (RFLP) analysis confirmed a homozygous mutation in NCF1. Given the absence of an HLA-matched donor, treatment with pioglitazone was initiated at 3 mg/kg/day. After two months, a significant improvement in DHR fluorescence was observed, indicating restored phagocytic function. The patient showed rapid clinical improvement, with a reduction in hospitalization frequency and no severe infections for six months. Conclusions This case demonstrates the effectiveness of pioglitazone in treating CGD due to NCF1 mutation, particularly in patients lacking suitable donors or facing delays in HSCT. The use of pioglitazone may represent a promising alternative treatment strategy for CGD, especially in resource-limited settings.