Table 1.

Genetic Disorders of Surfactant Metabolism

	Surfactant Protein B Deficiency	ABCA3 Deficiency Neonate	ABCA3 Deficiency Infant	ABCA3 Deficiency Child	Surfactant Protein C Associated Lung Disease	NKX2-1 Deficiency Neonate	NKX2-1 Deficiency Child
Presentation	Acute severe neonatal respiratory distress (RDS) shortly after birth5	Acute severe neonatal RDS shortly after birth35	Respiratory distress or interstitial lung disease (chILD) between 1month and 1 year35	Interstitial lung disease (chILD) after 1 year of life35	Interstitial lung disease (chILD) and/or failure to thrive during infancy and childhood; less commonly as neonatal RDS10	Acute severe neonatal RDS shortly after birth, hypothyroidism, hypotonia16	Interstitial lung disease (chILD), recurrent respiratory infections, chorea, ataxia, developmental delay, hypothyroidism16
Frequency	1 per million European-descent (ED)4	As frequent as 1/3100 ED; as frequent as 1/18,000 African-descent (AD)13	As frequent as 1/3100 ED; as frequent as 1/18,000 AD13	As frequent as 1/3100 ED; as frequent as 1/18,000 AD13	Unknown4	Unknown16	Unknown16
Disease Course	Lethal in newborn period5	Lethal for infants with 2 loss of function (frameshift, nonsense) mutations, variable for other genotypes35	Variable35	Variable35	Variable22	Variable16	Variable16
Inheritance	Recessive/compound heterozygous	Recessive/compound heterozygous	Recessive/compound heterozygous	Recessive/compound heterozygous	Dominant, sporadic	Dominant, sporadic	Dominant, Sporadic