Information Sheet: Surfactant Protein C Mutations (Interstitial Lung Disease) From the Rare Lung Diseases Program, Cincinnati Children’s Hospital Medical Center
What is Interstitial Lung Disease? Interstitial Lung Disease (ILD) is a term that refers to a group of lung disorders with many different causes. The “interstitium” is the space in the lung between the alveoli (air sacs) where oxygen enters the blood circulation and carbon dioxide is released. Pulmonary fibrosis is a type of ILD in which there is scarring in the lung. Surfactant protein C (SP-C) mutations are an extremely rare cause of ILD and pulmonary fibrosis. “Familial pulmonary fibrosis” refers to pulmonary fibrosis when 2 or more members of the same family are affected. The prevalence of familial pulmonary fibrosis is estimated to be between 1.34 and 5.9 cases per million population. SP-C mutations are one cause of familial pulmonary fibrosis. What is surfactant? In order for the lungs to work properly, they need to make a substance known as surfactant to prevent them from collapsing at the end of a breath. Premature babies often have breathing problems because their lungs do not make surfactant yet. However, some children (and adults) have lung problems due to problems with their lung surfactant. There are certain proteins that the lungs make which are important in how this surfactant material is able to do its job. Surfactant protein C (SP-C) is one of these proteins which is needed for normal lung function. Others that have been found are called Surfactant Protein B (SP-B) and ABCA3. People who are missing one of these proteins due to changes in their genes develop breathing problems. Genes contain the instructions for how a protein is made. A mutation refers to an alteration or change in a gene that causes the protein not to be made, or alters the resulting protein that is made such that it may not function properly. Surfactant protein C is made only in alveolar type II cells in the lung, so other organs in the body are not directly affected in this disease. What are the symptoms of SP-C lung disease? SP-C disease can have highly variable clinical presentations, even in members of the same family. Children with ILD often have chronic fast breathing (tachypnea) and retractions, and many require supplemental oxygen. Chest X-rays and CT scans typically show diffuse abnormalities. Patients can present with severe symptoms in the first few months of life, can present with symptoms in adulthood, or they may even remain asymptomatic. Shortness of breath, chronic cough, recurrent pneumonia, or other breathing difficulties can be signs of SP-C lung disease. Specific types of lung disease due to SP-C mutations can include alveolar proteinosis in young children, or various forms of ILD including pulmonary fibrosis. How is Surfactant Protein C disease inherited? Sometimes SP-C disease occurs sporadically, which means it was not inherited. More often, mutations (genetic abnormalities) in the surfactant protein C gene (SFTPC) are inherited in an autosomal dominant manner. Dominant inheritance means an abnormal gene from one parent is capable of causing disease, even though the matching gene from the other parent is normal. The abnormal gene "dominates" the pair of genes. If just one parent has a dominant gene defect, each child has a 50% chance of inheriting the disorder. Over 50 different SP-C mutations have been found in SP-C disease.
How is SP-C lung disease diagnosed? Diagnosis of SFTPC mutations is through genetic testing, generally done from a blood sample. This can be done as a clinical test at very specialized labs (www.genetests.org) or on a research basis. Clinical results are typically available in 3-4 weeks, but may take longer from research labs. Before undergoing genetic testing for SP-C, you should talk with a doctor or genetic counselor knowledgeable about this disorder. Some individuals may be asymptomatic, and genetic counseling should be offered to families with this diagnosis or who are considering testing for SP-C. If someone is diagnosed with an SP-C mutation or thinks they may have SP-C lung disease, they should see a pulmonary specialist. In addition to assessing for symptoms of lung disease, other tests of lung health can include pulmonary function tests, chest x-rays and chest CT scans, and oxygen testing during exercise. Lung biopsies are generally not needed once an individual is known to have an SP-C mutation. What is prognosis and treatment for SP-C lung disease? The prognosis and outcome are not well understood, in part because it is a rare disorder and there is so much variability even within a single family. SP-C lung disease can be fatal in children and adults. Some children with SFTPC mutations have undergone lung transplantation. Others have had severe respiratory compromise but gradually improved over time. Again, it is important to remember that some individuals with SP-C mutations can remain symptom-free. Many things may influence the outcome of SP-C disease. Different SP-C mutations may have different prognoses. Viral infections and other exposures such as tobacco smoke may also worsen or may even trigger the disease. It is very important to avoid further injuries to the lungs, such as from infections or gastroesophageal reflux. Currently, there are no proven treatments. Hydroxychloroquine has been tried in some pediatric cases. Corticosteroids are sometimes used. New therapies are being tested in the laboratory and in clinical trials for other forms of pulmonary fibrosis. General supportive care for individuals with SFTPC mutations includes supplemental oxygen as needed, and monitoring and treatment for pulmonary hypertension if present. Good nutrition and monitoring of growth are particularly important for infants with ILD, as extra calories are often needed due to fast breathing. In addition to routine childhood immunizations, Synagis (RSV prophylaxis) is recommended for infants and young children. Many researchers at Cincinnati Children’s Hospital Medical Center are currently studying surfactant protein C related lung disease. To learn more, please contact: Lisa R. Young, MD Assistant Professor of Pediatrics and Medicine Director, Pediatric Rare Lung Diseases Program Division of Pulmonary Medicine Cincinnati Children’s Hospital Medical Center (513) 636-6771