Prenatal diagnosis of congenital alveolar proteinosis (surfactant protein B deficiency)

We report on the DNA-based prenatal diagnosis of congenital pulmonary alveolar proteinosis in a family in which alveolar proteinosis was associated with surfactant protein B (SP-B) deficiency. The parents had lost an eight-week-old female child due to this fatal disorder. The affected child was homozygous and both parents were heterozygous for a frame-shift mutation in codon 121 of the surfactant protein B gene (SFTP3-gene). Chorionic villus sampling (CVS) was performed in two subsequent pregnancies. DNA analysis revealed homozygosity for the codon 121 mutation in the first fetus, and the pregnancy was terminated. Homozygosity for the parental wild-type alleles was detected in the following prenatal diagnosis, and a healthy child has been born. DNA-based prenatal diagnosis of congenital alveolar proteinosis is simple, fast and reliable, and can be performed much earlier in pregnancy than any other method, e.g. the direct measurement of SP-B in amniotic fluid. In families with a term infant who dies of unexplained respiratory failure, genetic testing of the parents should be evaluated, since the presence of the codon 121 mutation enables prenatal diagnosis in later pregnancies.