Mutations in the ABCA3 gene can result in fatal surfactant deficiency in term newborn infants and chronic interstitial lung disease in older children.
CT scans commonly reveal ground-glass opacification, septal thickening, parenchymal cysts and pectus excavatum.
Histopathological patterns included pulmonary alveolar proteinosis, desquamative interstitial pneumonitis and non-specific interstitial pneumonitis, and varied with age.
Dense abnormalities of lamellar bodies, characteristic of ABCA3 mutations, were seen by electron microscopy in all adequate specimens.
Outcomes vary with the age at which the severity of lung disease warranted open lung biopsy.
Some patients have had prolonged survival without lung transplantation.
The presentation and course of interstitial lung disease due to ABCA3 mutations are variable, and open lung biopsy and genetic testing are warranted early in the evaluation of children with a consistent clinical picture.
Ultrastructure
Electron microscopy of alveolar type 2 cells demonstrates abnormal lamellar body formation.
Variants
Fatal familial lung disease caused by ABCA3 deficiency without identified ABCA3 mutations. (20304423)
See also
ABCA3-associated alveolar proteinosis
ABCA3-associated fatal neonatal interstitial pneumonia (17660803)
ABCA3-associated respiratory distress (17618459)
ABCA3-associated congenital surfactant deficiency (16316951)
ABCA3-associated unexplained neonatal respiratory distress (UNRD)
ABCA3 gene
References
Fatal Familial Lung Disease Caused by ABCA3 Deficiency without Identified ABCA3 Mutations. Gower WA, Wert SE, Ginsberg JS, Golan A, Whitsett JA, Nogee LM. J Pediatr. 2010 Mar 19. PMID: 20304423
Doan ML, Guillerman RP, Dishop MK, Nogee LM, Langston C, Mallory GB, Sockrider MM, Fan LL. Clinical, radiological and pathological features of ABCA3 mutations in children. Thorax. 2008 Apr;63(4):366-73. Epub 2007 Nov 16. PMID: 18024538
Bruder E, Hofmeister J, Aslanidis C, Hammer J, Bubendorf L, Schmitz G, Rufle A, Bührer C. Ultrastructural and molecular analysis in fatal neonatal interstitial pneumonia caused by a novel ABCA3 mutation. Mod Pathol. 2007 Oct;20(10):1009-18. PMID: 17660803
Bullard JE, Nogee LM. Heterozygosity for ABCA3 mutations modifies the severity of lung disease associated with a surfactant protein C gene (SFTPC) mutation. Pediatr Res. 2007 Aug;62(2):176-9. PMID: 17597647
Yokota T, Matsumura Y, Ban N, Matsubayashi T, Inagaki N. Heterozygous ABCA3 mutation associated with non-fatal evolution of respiratory distress. Eur J Pediatr. 2007 Jul 6;PMID: 17618459
Saugstad OD, Hansen TW, Rønnestad A, Nakstad B, Tølløfsrud PA, Reinholt F, Hamvas A, Coles FS, Dean M, Wert SE, Whitsett JA, Nogee LM. Novel mutations in the gene encoding ATP binding cassette protein member A3 (ABCA3) resulting in fatal neonatal lung disease. Acta Paediatr. 2007 Feb;96(2):185-90. PMID: 17429902
Edwards V, Cutz E, Viero S, Moore AM, Nogee L. Ultrastructure of lamellar bodies in congenital surfactant deficiency. Ultrastruct Pathol. 2005 Nov-Dec;29(6):503-9. PMID: 16316951
Clark H, Clark LS. The genetics of neonatal respiratory disease. Semin Fetal Neonatal Med. 2005 Jun;10(3):271-82. PMID: 15927881