A Case of Female X-linked Chronic Granulomatous Disease Caused by X Chromosome Inactivation Treated with...

Area of Science:

• Immunology
• Genetics
• Hematology

Background:

• X-linked chronic granulomatous disease (X-CGD) is a rare primary immunodeficiency characterized by phagocyte dysfunction, typically caused by CYBB gene mutations in males.
• While predominantly affecting males, female carriers can present with X-CGD due to skewed X chromosome inactivation.

Purpose of the Study:

• To investigate X-CGD in a rare case involving an infant and a young woman.
• To provide insights into the diagnosis and treatment of X-CGD, particularly in female carriers.

Main Methods:

• Assessment of neutrophil respiratory burst function and gp91phox protein expression.
• Whole exon gene analysis and X chromosome inactivation evaluation.
• Hematopoietic stem cell transplantation (HSCT) using haploidentical family donors.

Main Results:

• Affected children carried the CYBB gene mutation with abnormal neutrophil function and absent gp91phox protein.
• X chromosome inactivation analysis showed a high rate (99.5%) of skewing.
• Successful engraftment post-HSCT led to normalized granulocyte/megakaryocyte function and laboratory markers.

Conclusions:

• X-CGD should be considered in the differential diagnosis of granulomatous disease in children and women.
• Hematopoietic stem cell transplantation demonstrates significant therapeutic efficacy for X-CGD.
• Early diagnosis and intervention, alongside optimized HSCT strategies, are crucial for improved patient outcomes.