Surfactant Panel (SFTPB, SFTPC, ABCA3)

Ambry's Surfactant Panel includes testing for mutations in three genes: SFTPB, SFTPC and ABCA3. The Surfactant Panel is a useful and efficient diagnostic tool for the investigation of severe neonatal respiratory distress and pediatric and familial interstitial lung diseases.

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Ambry's Surfactant Panel includes testing for mutations in three genes: SFTPB, SFTPC and ABCA3. The Surfactant Panel is a useful and efficient diagnostic tool for the investigation of severe neonatal respiratory distress and pediatric and familial interstitial lung diseases.

Surfactant proteins are critical for pulmonary health as they manage infectious challenges and the biomechanical stresses of oxygen exchange on the lung tissue. Genetic testing for defects in three genes (SFTPB, SFTPC and ABCA3) is a useful diagnostic tool for the investigation of severe neonatal respiratory distress and interstitial lung diseases.

Inherited Surfactant Protein B Deficiency is caused by autosomal recessive mutations of the SFTPB gene that result in atelectasis and respiratory failure in full-term infants. Defects in the Surfactant Protein C SFTPC gene can manifest as one of many different interstitial lung disease (ILD) diagnoses across a wide range of onset ages, even within the same family. Clinical and histological presentation of ABCA3 gene mutations may be similar to that of either Surfactant Protein B Deficiency or Surfactant Protein C Deficiency. Mutations are typically inherited in an autosomal recessive pattern and are a significant cause of both neonatal respiratory failure and pediatric ILD.

The Surfactant Panel includes gene sequence analysis of all translated regions of the SFTPB, SFTPC and ABCA3 genes that detects approximately 99% of known mutations.

Tests for each individual gene can also be ordered separately or in sequence according to the physician’s preference.

Disease Name 
Surfactant Dysfunction
Interstitial Lung Disease, Pediatric and Familial
Neonatal Respiratory Failure
Postnatal Respiratory Distress (chronic
Disease Information 

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. Defects in production, processing, and transport of surfactant components have been associated with a wide range of diagnoses.1,2 Genetic testing for defects in three genes (SFTPB, SFTPC and ABCA3) is a useful and efficient diagnostic tool for theinvestigation of severe neonatal respiratory distress and interstitial lung diseases.

Surfactant Protein B (SP-B) has a critical role in stabilizing and enhancing rapid spreading of the surfactant phospholipid layer to reduce surface tension in the alveoli. Inherited Surfactant Protein B Deficiency is caused by autosomal recessive mutations of the SFTPB gene that result in atelectasis and respiratory failure in full-term infants. Rare cases of SP-B mutations resulting in severe disease with longer survival have been reported.3 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) has a similar role in reducing surface tension. Defects in the SFTPC gene can manifest as one of many different diagnoses across a wide range of onset ages, even within the same family. SP-C related disease has presented as chronic or nonspecific interstitial pneumonitis 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 (ILD).4-6 Familial cases with dominant inheritance of mutations and sporadic cases with de novo mutations have been described.5,6
 
ABCA3 protein is involved in the formation of lamellar bodies which transport surfactant phospholipids and proteins from their production site to the alveolar space.7 Clinical and histological presentation of ABCA3 gene mutations may be similar to that of either SP-B or SP-C deficiencies. Mutations are typically inherited in an autosomal recessive pattern and are a significant cause of both neonatal respiratory failure8 and pediatric ILD.9 Research on the interactions of these genes is unfolding. The co-occurrence of a heterozygous ABCA3 mutation and the SFTPC mutation I73T in three infantile-onset pediatric ILD patients whose asymptomatic parents each carried only one of the two mutations suggests that ABCA3 mutations may modify the severity of the SFTPC mutation.10
Testing Benefits & Indication 

DNA sequence analysis of surfactant genes provides the following advantages over other diagnostic tests:

  • results are not affected by prematurity or the disease process
  • done on easily-collected whole blood, bloodspot, or saliva sample
  • enables appropriate counseling of patients and family members

Clinical indications for testing are:

  • respiratory failure in full-term newborns
  • chronic respiratory distress after the newborn period
  • pediatric interstitial disease, especially chronic pneumonitis of infancy (CPI), desquamative interstitial
  • pneumonitis (DIP), and non-specific interstitial pneumonitis (NSIP)
  • adult interstitial lung disease with family history, including pulmonary fibrosis
  • follow-up to abnormal histology or BAL/tracheal aspirate analysis
  • carrier screening in parents of full-term newborn with unexplained respiratory failure
Specimen Requirements 

Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (rst choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Minimum of one complete spot approximately 0.5 inch in diameter on S&S 903 collection paper or similar. Store in a clean plastic bag at room temperature. Ship at room temperature.
Saliva: Collect 2 ml into OrageneTM DNA Self-Collection container. Store and ship at room temperature.
DNA: Minimum DNA Amount of 5μg of DNA at a concentration of ~100ng/μl in 50μl TE (10mM Tris-Cl pH 8.0, 1mM EDTA); preferred 20μg. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available for the indication Surfactant deciency. Please call an Ambry Genetic Counselor to discuss your case.

Billing Codes 
Test Code Technique
1300 ABCA3 Gene Sequence Analysis
1160 SFTPB Gene Sequence Analysis
1180 SFTPC Gene Sequence Analysis
8100 Surfactant Panel (ABCA3, SFTPB and SFTPC gene sequence) (concurrent)

 

Updated CPT Codes for 2013
Turnaround Time 
Technique Days
ABCA3 Gene Sequence Analysis 7-14
SFTPB Gene Sequence Analysis 5-10
SFTPC Gene Sequence Analysis 5-10
Surfactant Panel (ABCA3, SFTPB and SFTPC gene sequence) (concurrent) 5-14

 

Specialty 
Pulmonology
Genes 
ABCA3
SFTPB
SFTPC
References 

1. Whitsett JA,Weaver TE. Hydrophobic surfactant proteins in lung function and disease. N Engl J Med. 2002;347:2141-2148. [PMID: 12501227]

2. Bullard JE et al. ABCA3 deficiency: neonatal respiratory failure and interstitial lung disease. Semin Perinatol. 2006;30:327-334. [PMID: 17142158]

3. Dunbar AE et al. Prolonged survival in hereditary surfactant protein B (SP-B) deficiency associated with a novel splicing mutation. Ped Research. 2000;48:275-282. [PMID: 10960490]

4. Thomas AQ et al. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Am J Resp Crit Care Med. 2002;165:1322-1328. [PMID: 11991887]

5. Nogee LM et al. A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med. 2001;344:573-579. [PMID: 11207353]

6. Cameron HS et al. A common mutation in the surfactant protein C gene associated with lung disease. J Pediatr. 2005;146:370-375. [PMID: 15756222]

7. Cheong N et al. Functional and trafficking defects in ATP binding cassette A3 mutants associated with respiratory distress syndrome. J Biol Chem. 2006;281:9791-9800. [PMID: 16415354]

8. Shulenin S et al. ABCA3 gene mutations in newborns with fatal surfactant deficiency. N Engl J Med. 2006;350:1296-1303. [PMID: 15044640]

9. Bullard JE et al. ABCA3 mutations associated with pediatric interstitial lung disease. Am J Resp Crit Care Med. 2005;172:1026-1031. [PMID: 15976379]

10. Bullard JE and Nogee LM. Heterozygosity for ABCA3 mutations modifies the severity of lung disease associated with a surfactant protein C gene (SFTPC) mutation. Ped Research. 2007;62:176-179. [PMID: 17597647]