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Surfactant metabolism dysfunction, pulmonary, 1(SMDP1)

MedGen UID:
368844
Concept ID:
C1968602
Disease or Syndrome
Synonyms: INTERSTITIAL LUNG DISEASE DUE TO SURFACTANT PROTEIN B DEFICIENCY; INTERSTITIAL LUNG DISEASE, NONSPECIFIC, DUE TO SURFACTANT PROTEIN B DEFICIENCY; Neonatal acute respiratory distress due to SP-B deficiency; PULMONARY ALVEOLAR PROTEINOSIS, CONGENITAL, 1; Pulmonary surfactant protein B, deficiency of
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SFTPB (2p11.2)
 
Monarch Initiative: MONDO:0009929
OMIM®: 265120
Orphanet: ORPHA217563

Definition

Inborn errors of pulmonary surfactant metabolism are genetically heterogeneous disorders resulting in severe respiratory insufficiency or failure in full-term neonates or infants. These disorders are associated with various pathologic entities, including pulmonary alveolar proteinosis (PAP), desquamative interstitial pneumonitis (DIP), or cellular nonspecific interstitial pneumonitis (NSIP) (Clark and Clark, 2005). A clinically similar disorder characterized by respiratory distress (267450) can affect preterm infants, who show developmental deficiency of surfactant. Acquired PAP (610910) is an autoimmune disorder characterized by the presence of autoantibodies to CSF2 (138960). Genetic Heterogeneity of Pulmonary Surfactant Metabolism Dysfunction See also SMDP2 (610913), caused by mutation in the SPTPC gene (178620) on 8p21; SMDP3 (610921), caused by mutation in the ABCA3 gene (601615) on 16p13; SMDP4 (300770), caused by mutation in the CSF2RA gene (306250) on Xp22; and SMDP5 (614370), caused by mutation in the CSF2RB gene (138981) on 22q12. [from OMIM]

Additional description

From MedlinePlus Genetics
Surfactant dysfunction is a lung disorder that causes breathing problems. This condition results from abnormalities in the composition or function of surfactant, a mixture of certain fats (called phospholipids) and proteins that lines the lung tissue and makes breathing easy. Without normal surfactant, the tissue surrounding the air sacs in the lungs (the alveoli) sticks together (because of a force called surface tension) after exhalation, causing the alveoli to collapse. As a result, filling the lungs with air on each breath becomes very difficult, and the delivery of oxygen to the body is impaired.

The signs and symptoms of surfactant dysfunction can vary in severity. The most severe form of this condition causes respiratory distress syndrome in newborns. Affected babies have extreme difficulty breathing and are unable to get enough oxygen. The lack of oxygen can damage the baby's brain and other organs. This syndrome leads to respiratory failure, and most babies with this form of the condition do not survive more than a few months.

Less severe forms of surfactant dysfunction cause gradual onset of breathing problems in children or adults. Signs and symptoms of these milder forms are abnormally rapid breathing (tachypnea); low concentrations of oxygen in the blood (hypoxemia); and an inability to grow or gain weight at the expected rate (failure to thrive).

There are several types of surfactant dysfunction, which are identified by the genetic cause of the condition. One type, called SP-B deficiency, causes respiratory distress syndrome in newborns. Other types, known as SP-C dysfunction and ABCA3 deficiency, have signs and symptoms that range from mild to severe.  https://medlineplus.gov/genetics/condition/surfactant-dysfunction

Clinical features

From HPO
Clubbing
MedGen UID:
57692
Concept ID:
C0149651
Anatomical Abnormality
Broadening of the soft tissues (non-edematous swelling of soft tissues) of the digital tips in all dimensions associated with an increased longitudinal and lateral curvature of the nails.
Pulmonary arterial hypertension
MedGen UID:
425404
Concept ID:
C2973725
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
Misalignment of the pulmonary veins
MedGen UID:
1739709
Concept ID:
C5421670
Anatomical Abnormality
The term is commonly used to describe a putative abnormal location of pulmonary vein branches adjacent to pulmonary arteries within the same adventitial sheath. However, evidence has been provided that the vessels in question are not pulmonary veins, however represent dilated bronchial veins.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Sign or Symptom
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Dyspnea
MedGen UID:
3938
Concept ID:
C0013404
Sign or Symptom
Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.
Tachypnea
MedGen UID:
66669
Concept ID:
C0231835
Finding
Very rapid breathing.
Desquamative interstitial pneumonia
MedGen UID:
65962
Concept ID:
C0238378
Disease or Syndrome
Interstitial lung disease (ILD), or pneumonitis, is a heterogeneous group of disorders characterized pathologically by expansion of the interstitial compartment of the lung by inflammatory cells. Fibrosis occurs in many cases (Visscher and Myers, 2006). See also interstitial lung disease-1 (ILD1; 619611). Desquamative interstitial pneumonitis (DIP) was originally described as a pathologic entity by Liebow et al. (1965). Lung biopsy shows diffuse and uniform filling of alveoli by clusters of cells which Liebow et al. (1965) speculated to be 'desquamated pneumocytes.' Since then, these cells have been shown primarily to be pigmented alveolar macrophages. Other features include thickened alveolar septa with an infiltrate of inflammatory cells and plump, cuboidal type II pneumocytes. Mild collagen deposition without architectural distortion or honeycombing may be present. Different forms of ILD represent pathologic classifications based on histologic patterns rather than clinical diagnoses and may occur in a variety of clinical contexts (Visscher and Myers, 2006). Although DIP occurs most often as a sporadic disorder in adults during the third to fifth decade of life and is highly associated with smoking (Carrington et al., 1978), reports of a familial form with onset in infancy and early death suggest a genetic basis (Sharief et al., 1994). Cases of DIP reported in infants are often more severe and refractory to treatment than those reported in adults (Nogee et al., 2001).
Respiratory failure
MedGen UID:
257837
Concept ID:
C1145670
Disease or Syndrome
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Absent bronchoalveolar dimeric surfactant-protein B
MedGen UID:
1714465
Concept ID:
C5397973
Finding
Significantly decreased level or failed detection of surfactant protein B in broncho-alveolar lavage fluid.
Pulmonary alveolar proteinosis
MedGen UID:
1763046
Concept ID:
C5400698
Finding
Accumulation of amorphous PAS-positive material in the space between alveolar macrophages, sometimes as condensed form (oval bodies) are typically found in alveolar proteinosis.
Ground-glass opacification
MedGen UID:
1779663
Concept ID:
C5539411
Finding
On chest radiographs, ground-glass opacity appears as an area of hazy increased lung opacity, usually extensive, within which margins of pulmonary vessels may be indistinct. On CT scans, it appears as hazy increased opacity of lung, with preservation of bronchial and vascular margins. It is caused by partial filling of airspaces, interstitial thickening (due to fluid, cells, and/or fibrosis), partial collapse of alveoli, increased capillary blood volume, or a combination of these, the common factor being the partial displacement of air. Ground-glass opacity is less opaque than consolidation, in which bronchovascular margins are obscured.
Interlobular septal thickening
MedGen UID:
1779791
Concept ID:
C5539418
Finding
Presence of thickening of the interlobular septa of the lungs as seen on a CT scan.
Cyanosis
MedGen UID:
1189
Concept ID:
C0010520
Sign or Symptom
Bluish discoloration of the skin and mucosa due to poor circulation or inadequate oxygenation of arterial or capillary blood.

Recent clinical studies

Etiology

Nattes E, Lejeune S, Carsin A, Borie R, Gibertini I, Balinotti J, Nathan N, Marchand-Adam S, Thumerelle C, Fauroux B, Bosdure E, Houdouin V, Delestrain C, Louha M, Couderc R, De Becdelievre A, Fanen P, Funalot B, Crestani B, Deschildre A, Dubus JC, Epaud R
Respir Med 2017 Aug;129:16-23. Epub 2017 May 26 doi: 10.1016/j.rmed.2017.05.014. PMID: 28732825

Diagnosis

Nattes E, Lejeune S, Carsin A, Borie R, Gibertini I, Balinotti J, Nathan N, Marchand-Adam S, Thumerelle C, Fauroux B, Bosdure E, Houdouin V, Delestrain C, Louha M, Couderc R, De Becdelievre A, Fanen P, Funalot B, Crestani B, Deschildre A, Dubus JC, Epaud R
Respir Med 2017 Aug;129:16-23. Epub 2017 May 26 doi: 10.1016/j.rmed.2017.05.014. PMID: 28732825
Griese M, Lorenz E, Hengst M, Schams A, Wesselak T, Rauch D, Wittmann T, Kirchberger V, Escribano A, Schaible T, Baden W, Schulze J, Krude H, Aslanidis C, Schwerk N, Kappler M, Hartl D, Lohse P, Zarbock R
Pediatr Res 2016 Jan;79(1-1):34-41. Epub 2015 Sep 16 doi: 10.1038/pr.2015.173. PMID: 26375475

Therapy

Nattes E, Lejeune S, Carsin A, Borie R, Gibertini I, Balinotti J, Nathan N, Marchand-Adam S, Thumerelle C, Fauroux B, Bosdure E, Houdouin V, Delestrain C, Louha M, Couderc R, De Becdelievre A, Fanen P, Funalot B, Crestani B, Deschildre A, Dubus JC, Epaud R
Respir Med 2017 Aug;129:16-23. Epub 2017 May 26 doi: 10.1016/j.rmed.2017.05.014. PMID: 28732825

Prognosis

Nattes E, Lejeune S, Carsin A, Borie R, Gibertini I, Balinotti J, Nathan N, Marchand-Adam S, Thumerelle C, Fauroux B, Bosdure E, Houdouin V, Delestrain C, Louha M, Couderc R, De Becdelievre A, Fanen P, Funalot B, Crestani B, Deschildre A, Dubus JC, Epaud R
Respir Med 2017 Aug;129:16-23. Epub 2017 May 26 doi: 10.1016/j.rmed.2017.05.014. PMID: 28732825

Clinical prediction guides

Griese M, Lorenz E, Hengst M, Schams A, Wesselak T, Rauch D, Wittmann T, Kirchberger V, Escribano A, Schaible T, Baden W, Schulze J, Krude H, Aslanidis C, Schwerk N, Kappler M, Hartl D, Lohse P, Zarbock R
Pediatr Res 2016 Jan;79(1-1):34-41. Epub 2015 Sep 16 doi: 10.1038/pr.2015.173. PMID: 26375475

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