Pulmonary surfactant is a mixture of lipids and proteins lining the surface of the lungs that facilitates air exchange. Surfactant proteins are critical for pulmonary health as they manage infectious challenges and the biomechanical stresses of oxygen exchange on the lung tissue. ABCA3 is involved in shuttling surfactant components from their production sites inside the lung cell to the surface of the alveoli. Genetic defects in production, processing, and transport of surfactant components have been associated with a range of pulmonary disease diagnoses.

Surfactant Protein B (SP-B) is a critical component of pulmonary surfactant. It stabilizes and enhances rapid spreading of the surfactant phospholipid layer to reduce surface tension in the alveoli. Autosomal recessive inheritance of genetic defects can cause deficiency of SP-B that results in atelectasis and neonatal respiratory failure in full-term infants. Rare cases of SP-B mutations resulting in severe disease with longer survival have been reported. Lung fluid and tissues of affected patients exhibit reduced or absent SP-B, accumulation of abnormal surfactant protein C precursor, and pulmonary alveolar proteinosis.

Surfactant Protein C (SP-C) also incorporates into the lipid layer to aid surfactant spreading and reduce alveolar surface tension. Genetic defects in SP-C are associated with several diagnoses with variable ages of onset within families and between unrelated patients. SP-C related disease has presented as chronic pneumonitis or nonspecific interstitial lung disease in infancy and childhood, as the usual and desquamative types of interstitial pneumonitis in early through late adulthood, and as other types of interstitial lung disease. Familial cases with dominant inheritance of mutations and sporadic cases with de novo mutations have been described.

ABCA3 maintains pulmonary surfactant homeostasis through transport of phospholipids and proteins to the alveolar surface. Mutations of ABCA3 are typically inherited in an autosomal recessive pattern and can cause severe neonatal respiratory distress characterized by deficiencies of mature surfactant proteins B and C. ABCA3 mutations have also been described in pediatric interstitial lung disease patients, including those with chronic pneumonitis of infancy, desquamative interstitial pneumonitis, and non-specific interstitial pneumonitis.

DNA sequence analysis of surfactant genes provides a result uncomplicated by effects of prematurity, the disease process, or invasive specimen collection.

Clinical indications for testing are:

• Respiratory failure in full-term newborn (SP-B, ABCA3)
• Carrier testing in parents of full-term newborn with unexplained respiratory failure (SP-B, ABCA3)
• Follow-up to abnormal histology or BAL/tracheal aspirate analysis (SP-B, SP-C, ABCA3)
• Chronic respiratory distress after the newborn period (SP-B,
  SP-C, ABCA3)
• Interstitial lung disease with family history (SP-C, ABCA3), including pulmonary fibrosis (SP-C)

The following tests are offered on a research basis. Please contact us for more information.

• Surfactant Protein A (SFTPA1 and SFTPA2 genes)
• Surfactant Protein D (SFTPD)
• Asthma (ADRB2 gene)

The Ambry Test: Surfactant Dysfunction

General Test Information
The Ambry Test: Surfactant Protein B Deficiency

General Test Information
The Ambry Test: Surfactant Protein C Deficiency

General Test Information
The Ambry Test: ABCA3

The following CPT Codes for The Ambry Test reflects Ambry Genetics’ interpretation of CPT coding requirements based on AMA guidelines:

Ambry Test: Surfactant Protein B (SFTPB)
83891, 83894, 83898, 83904, 83909, 83912

Ambry Test: Surfactant Protein C (SFTPC)
83891, 83894, 83898, 83904, 83909, 83912

Ambry Test:ABCA3
83891, 83894, 83898, 83904, 83909, 83912

CPT codes are provided only as a guide to assist you in billing. CPT coding is the sole responsibility of the billing party.

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Disclaimer:

This test was developed and its performance characteristics were determined by Ambry Genetics Corporation. The laboratory is regulated under the Clinical Laboratory Improvement Amendments 2003 as qualified to perform nonwaived testing. Although molecular tests are highly accurate, rare diagnostic errors may occur. The Ambry Test analyzes the following types of mutations (nucleotide substitutions, small deletions, small insertions, and small indels) and is not intended to analyze the following types of mutations (gross insertions, gross deletions, gross rearrangements, and other unknown abnormalities). The pattern of mutation types varies with the gene tested and the Ambry Test detects a high but variable percentage of known and unknown mutants of the classes stated. A negative result from the analysis cannot rule out the possibility that the tested individual carries a rare unexamined mutation or mutation in the undetectable group. The Ambry Test: SFTPB/SFTPC/ABCA3 is designed and validated to be capable of detecting ~99% of Surfactant Protein B/C or ABCA3 mutations (considering the other ~1% to be gross abnormalities, variants in non-coding regions including introns, untranslated sequences, and 5’UTR, or unknown abnormalities). Surfactant Protein B/C and ABCA3 Deficiencies are complex clinical disorders, which in the majority of cases are due to alterations in the Surfactant Protein B/C or ABCA3 genes generally detected by the Ambry Test: SFTPB/SFTPC/ABCA3 except as noted above. Mutations in other genes or non-coding regions not tested by the Ambry Test: SFTPB/SFTPC/ABCA3 can also give rise to clinical conditions similar or identical to Surfactant Protein B/C or ABCA3 Deficiencies. Possible diagnostic errors include sample mix-up, erroneous paternity identification, technical errors, and genotyping errors. Genotyping errors can result from trace contamination of PCR reactions, from maternal cell contamination in fetal samples, from rare genetic variants, which interfere with analysis, or from other sources. This report does not represent medical advice. Any questions, suggestions, or concerns regarding interpretation of results should be forwarded to a genetic counselor, medical geneticist, or physician skilled in interpretation of the relevant medical literature. References are available upon request.