[A case of pulmonary alveolar proteinosis secondary to GATA2 deficiency combined with splenic M. kansasii infection and literature review].

Objective

To enhance the understanding of the rare disease GATA2 deficiency syndrome leading to pulmonary alveolar proteinosis (PAP) and non-tuberculous mycobacterial (NTM) disease.

Methods

The clinical data of a patient with GATA2 deficiency-associated PAP and splenic M. kansasii disease admitted to Peking University People's Hospital were summarized. Relevant literature from January 1, 2010 to March 31, 2025 was retrieved and reviewed through Wanfang Data, China National Knowledge Infrastructure, and the National Center for Biotechnology Information database.

Results

The patient was a 19-year-old male. The clinical manifestations included recurrent fever for 7 years. The peripheral blood routine test showed peripheral blood pancytopenia accompanied by monocytopenia. The serum granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody was negative. Chest CT revealed diffuse interstitial lung changes, while 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) demonstrated splenomegaly with multiple focal FDG-avid lesions. Bone marrow biopsy indicated marrow failure. Histopathological examination of lung biopsy specimens was consistent with alveolar proteinosis, whereas histopathology of the spleen biopsy revealed granuloma and patellar necrosis. Metagenomic next-generation sequencing (mNGS) of the splenic specimen detected M. kansasii, and genetic testing identified a germline GATA2 mutation(c.1128del, p.Y377fs). Based on these findings, a diagnosis of GATA2 deficiency with secondary PAP and splenic M. kansasii infection was established. Following anti-NTM treatment, the patient's infection was controlled; however, hematopoietic stem cell transplantation was planned due to bone marrow failure. Literature search revealed 4 cases of GATA2 deficiency syndrome with bone marrow dysplasia. Three cases developed PAP. All 4 cases had NTM infection, including 1 case with disseminated NTM infection in the lungs, spleen, and bone marrow. GATA2 deficiency syndrome patients are prone to decreased numbers and functional defects of cells such as monocytes and NK cells, resulting in immune dysfunction and pulmonary alveolar macrophage dysfunction, reduced ability to resist NTM, leading to the patient being prone to NTM infection, namely MonoMAC syndrome, and can cause secondary PAP. Early identification and timely completion of genetic testing are beneficial for clear diagnosis and establishment of precise intervention strategies.

Conclusion

GATA2 deficiency is a rare autosomal dominant genetic disorder caused by mutations in the GATA2 gene. Patients with cytopenia, GM-CSF antibody-negative PAP accompanied by NTM infection should be considered to have the possibility of this disease. Those patients should undergo GATA2 gene screening. Hematopoietic stem cell transplantation is currently the only possible method for curing GATA2 deficiency.