Case report: GATA-2 deficiency and secondary alveolar proteinosis (AP)

After suffering from various infections (mainly pneumonias) since 2007, in 2014 GATA-2 deficiency was diagnosed in a middle-aged female patient (pt).

In 2015 the pt was hospitalized with increasing exertional dyspnea and signs of infection (fever, elevated C-reactive protein). Lung function test showed moderate restriction with mildly reduced CO-diffusion capacity. The differential blood count of the peripheral blood (pb) detected less than 300 lymphocytes/µl. CT scan of the chest showed ground-glass infiltrates. Supposing an underlying organizing pneumonia various microbiological, virological and fungal tests (mycobacterium, mycoplasma, pneumocystis carinii, respiratory-, cytomegaly-, ebstein-bar-virus, ß-D-glucan, aspergillus antigen) were performed. All showing a negative result, explaining that various antibiotics were without benefit. The bronchoscopies showed milky-muddy bronchoalveloar lavage (BAL), high total cell amount (20 – 80 × 10⁶) and high neutrophil count (> 60%). Histology was compatible with AP. In cytology many protein precipitates were seen. Primary AP was excluded by negative testing of Anti-GM-CSF antibodies in the BAL and the pb. A therapeutic lavage with 12 Liter of physiologic salt solution of the left side of the lung was performed without benefit. Despite the lavage higher levels of oxygen administration (5 – 7 liters per minute (lpm)) were needed and fever was persisting. Supposing an anti-inflammatory effect application of an anti-IL-1-receptor antagonist was tried. The fever stopped immediately and oxygen administration could be reduced to 1 – 2 lpm.

Allogeneic stem cell transplantation as the only therapy for GATA-2 deficiency was refused by the pt at that time. Shortly thereafter the pt developed a severe septic shock and respiratory failure. Atypical mycobacteriae and high levels of aspergillus antigen were detected. Despite adequate antiinfective therapy and ECMO-support the pt died of cardiocirculatory arrest.

In conclusion, in secondary AP therapeutic lavage seems not to be a helpful option. Multidisciplinary treatment is needed in these pts.