Homozygous mutation in ABCA3 Lipid-Transporter defect (EXON 9) and low level of surfactant protein C

Background: Persistent ventilator dependency with 40% to 100% FiO₂ in a female baby born at term now seven months old. Objective: Due to ongoing tachypnoe, CPAP and oxygen dependency since birth and CT scan appearance a congenital defect in surfactant synthesis was evaluated. Methods: Bronchoalveolar lavage: Surfactant protein (SP-) C was reduced to about 1/7 of the amount normally present in relation to the content of SP-B and was thus severely reduced. In the genetic analysis no mutations in SFTPB, SFTPC and CSF2RA genes were found. However, a homozygous loss-of-function mutation in the coding region of the lipid transporter ABCA3 gene (Exon 9: Trp 308Arg, tgg/cgg(c.922T>C) was detected. Results: This mutation in the ABCA3 gene has not been described as a mutation or known polymorphism causing surfactant deficiency so far. To prove this hypothesis a lung biopsy should be performed for analysis of abnormal lamellar bodies in pulmonary type II cells. This is a typical feature seen in other patients with mutations in the ABCA3 transporter. Treatment with hydoxychloroquinsulfate was initiated. Conclusion: This mutation in ABC3 gene is probably the cause of surfactant deficiency; if possible evaluation by lung biopsy should be aimed at.