SMDP4 is an interstitial lung disorder characterized by the accumulation of surfactant protein exudate in the alveoli. This results in tachypnea, dyspnea, hypoxemia, a failure to thrive and eventually acute respiratory distress or respiratory failure. Pulmonary alveolar proteinosis (PAP) can occur in one of three forms: Congenital-PAP caused by certain gene mutations, Acquired-PAP caused by neutralizing autoantibodies to CSF2, or Secondary-PAP that occurs as a secondary complication of other conditions. SMDP4 is a congenital form of PAP that is caused by mutations in the CSF2RA gene. PAP is a rare disorder with an estimated incidence rate of 0.1 per 100,000 individuals. Congenital PAP forms a small subset of these, with CSF2RA-associated-PAP being reported in only a handful of cases. Individuals with SMDP4 may exhibit symptoms in early childhood. The disorder may also be triggered by factors such as respiratory tract infections.
Diagnosis is made based on clinical examinations, chest CT scans showing a characteristic ‘crazy paving’ pattern and bronchoscopy studies revealing milky bronchoalveolar lavage positive for periodic acid–Schiff stain. So far, whole lung lavage treatment has been very effective in improving respiratory function in SMDP4 patients. Other treatment options that are currently being researched include pulmonary macrophage transplantation and gene therapy.