Abstract

Background: Bi-allelic ABCA3 mutations are associated with heterogeneous phenotypes, from lethal neonatal respiratory distress to pediatric and rarely adult interstitial lung disease (ILD). We present a 24 years follow-up of a patient with ILD due to ABCA3 deficiency.

Case presentation: Patient’s history started at the age of 1.5 with frequent lower respiratory tract infections complicated by the age of 3 with respiratory failure. Chest CT revealed an ILD with ground glass opacities (GGOs) and the rest of the work up was negative. She underwent open lung biopsy at 5.5 years showing cellular interstitial pneumonia. Because no response to corticosteroids was observed she was treated with hydroxychloroquine (HCQ) with significant clinical and radiological amelioration until the age of 24 when it was interrupted due to retinopathy. At 26 years, the patient was in a good condition, non-smoker, with dyspnea on exertion. FVC, TLC and DLCO were 64%, 55%, and 35.5% pred. respectively. Heart U/S was normal. She desaturated from 98% to 92% walking 612 meters on 6MWT. CT demonstrated slightly deteriorated GGOs compared to two years ago. A second lung biopsy was performed setting the diagnosis of desquamative and non-specific interstitial pneumonia. Due to the young age of the ILD onset, the patient underwent genetic testing for surfactant disorders. Two non-null frameshift ABCA3 mutations were identified, each carried by one of her parents.  Patient initiated treatment with azithromycin and is stable at follow-up.

Discussion and conclusion: We present a rare case of an ILD patient compound heterozygous for ABCA3 mutations who survived from childhood to adulthood. Treatment options included HCQ and macrolides.