IllnessPulmonal surfactant protein anomaly, differential diagnosis

NGS +

Surfactant dysfunction causes breathing problems and results from abnormalities in the composition or function of surfactant, a mixture of certain phospholipids and proteins. Symptoms can vary in severity. The most severe form causes respiratory distress syndrome in newborns, with extreme difficulty breathing and oxygen deprivation. This syndrome leads to respiratory failure, and most infants with this form do not survive more than a few months. Less severe forms of surfactant dysfunction cause gradual onset of respiratory problems with tachypnea, hypoxemia and failure to thrive in children or adults. Surfactant dysfunction is caused by mutations in one of several genes, including SFTPA2, SFTPB, SFTPC, ABCA3, and others. If the disease is caused by mutations in the SFTPB or ABCA3 gene, it is inherited in an autosomal recessive manner. If the disease is caused by mutations in the SFTPA2 or SFTPC gene, it is inherited in an autosomal dominant manner. Mutation frequencies vary widely in pediatric cohorts with respiratory distress syndrome, monogenic surfactant-related disease appears to cause 10-20% of cases. Therefore, a negative DNA test result cannot exclude the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK1230/

https://err.ersjournals.com/content/30/159/200085

• Alias: Neuroendocrine cell hyperplasia of infancy
• Alias: Prim. interstit. Lungenerkrankung im Kindesalter durch pulmonale Surfactant-Protein-Anomalie
• Allelic: Chorea, hereditary benign (NKX2-1)
• Choreoathetosis, hypothyroidism + neonatal respiratory distress (NKX2-1)
• Pulmonary fibrosis, idiopathic (SFTPA2)
• Surfactant metabolism dysfunction, pulmonary, 1 (SFTPB)
• Surfactant metabolism dysfunction, pulmonary, 2 (SFTPC)
• Surfactant metabolism dysfunction, pulmonary, 3 (ABCA3)
• Surfactant metabolism dysfunction, pulmonary, 4 (CSF2RA)
• Surfactant metabolism dysfunction, pulmonary, 5 (CSF2RB)