What is ABCA3 disease?
ABCA3 transporter deficiency is a genetic disorder that is increasingly recognized as a cause of RDS in term babies in whom congenital deficiency of surfactant B and abnormalities of surfactant protein C have been excluded. It should be considered in mature babies who develop severe RDS.
What is the job of a surfactant?
The main functions of surfactant are as follows: (1) lowering surface tension at the air–liquid interface and thus preventing alveolar collapse at end-expiration, (2) interacting with and subsequent killing of pathogens or preventing their dissemination, and (3) modulating immune responses.
What is surfactant in lungs?
Surfactant is released from the lung cells and spreads across the tissue that surrounds alveoli. This substance lowers surface tension, which keeps the alveoli from collapsing after exhalation and makes breathing easy.
What is surfactant protein deficiency?
Surfactant protein B (SP-B) deficiency is an inherited disease of full-term newborn infants which leads to lethal respiratory failure within the first year of life and is refractory to mechanical ventilation, surfactant therapy, glucocorticoid induction of SP-B production, and extracorporeal membrane oxygenation.
What is another name for ABCA1?
ABCA1, also known as cholesterol efflux regulatory protein (CERP), functions as a cholesterol membrane transporter involved in the regulation of cellular cholesterol and phospholipid homeostasis. It has been shown that ABCA1 mediates the traffic of lipids between Golgi and cell membrane.
Why is surfactant important in the lungs?
Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with a relatively unique phospholipid, termed dipalmitoylphosphatidylcholine, and four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D.
Are surfactants harmful?
While soaps and surfactants differ in their composition and cleaning chemistry, their health hazards are similar. Both can disrupt lipid membranes that protect cells, and this causes irritation to skin, eyes, and respiratory systems.
Which problem is caused by a lack of pulmonary surfactant?
Reduction of the surface tension at the air–liquid interface is a requirement for respiratory function following birth. Deficiency of pulmonary surfactant causes respiratory failure in premature infants, or infantile respiratory distress syndrome (IRDS).
How is surfactant deficiency diagnosed?
The diagnosis is made by genetic testing for the mutation in the child and both parents. SP-B deficiency carries a poor prognosis and children with this disorder do not survive beyond the first few months of life. The only effective treatment is lung transplantation.
What does ABCA1 gene do?
The ABCA1 gene belongs to a group of genes called the ATP-binding cassette family, which provides instructions for making proteins that transport molecules across cell membranes. The ABCA1 protein is produced in many tissues, with high amounts found in the liver and in immune system cells called macrophages.
What is the cellular function for ABCA1?
ABCA1 mediates the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins (apoA1 and apoE) (reverse cholesterol transport), which then form nascent high-density lipoproteins (HDL). It also mediates the transport of lipids between Golgi and cell membrane.
What does the ABCA3 gene do?
Learn more The ABCA3 gene provides instructions for making a protein involved in surfactant production. Surfactant is a mixture of certain fats (called phospholipids) and proteins that lines the lung tissue and makes breathing easy.
Is the ABCA3 gene mutated in some infants with surfactant deficiency?
To test the hypothesis that the ABCA3 gene is mutated in some infants with surfactant deficiency, we sequenced each of the coding exons of the gene and the flanking splice sites in samples from 21 infants. Polymorphisms identified in this study were first used to assess the concordance of the six pairs of siblings for ABCA3 haplotypes.
Are lamellar bodies affected by ABCA3 mutations?
Markedly abnormal lamellar bodies were observed by ultrastructural examination of lung tissue from four patients with different ABCA3 mutations, including nonsense, splice-site, and missense mutations. Mutation of the ABCA3 gene causes fatal surfactant deficiency in newborns.
What are the haplotypes of ABCA3 polymorphisms?
The haplotype of ABCA3 polymorphisms is shown below each child (triangular symbols) in the pedigree. In Family 6, the two siblings are discordant for ABCA3 haplotypes, ruling out this gene as the cause of the disorder. All other families have at least one mutation identified in the gene.