Chronic respiratory distress with surfactant metabolism deficiency is a rare lung disease that mainly affects babies and children. In this disease, the lungs do not make or handle surfactant in a normal way. Surfactant is a slippery mix of fats and proteins that lines the tiny air sacs (alveoli) and helps them stay open when we breathe out. When surfactant is abnormal, the air sacs collapse, the lungs become stiff, and breathing becomes hard all the time. This long-term breathing trouble is called “chronic respiratory distress.” Most cases are caused by changes (mutations) in genes that control surfactant proteins or surfactant transport.
Chronic respiratory distress with surfactant metabolism deficiency is a rare, usually genetic lung disease where the body cannot make or process surfactant properly. Surfactant is a slippery, fat-rich substance that lines the tiny air sacs (alveoli) and stops them from collapsing when you breathe out. When surfactant is abnormal or too low, the alveoli collapse, the lungs become stiff, and it is hard to get oxygen into the blood, causing long-lasting breathing problems. Many children have mutations in genes such as SFTPB, SFTPC, ABCA3 or NKX2-1, which change surfactant proteins or their transport, leading to chronic interstitial lung disease and respiratory failure.
In surfactant metabolism deficiency, gene mutations stop type II alveolar cells from making normal surfactant proteins B and C or from packaging them correctly into storage bodies. The abnormal surfactant cannot lower surface tension, so water on the inner surface of alveoli pulls them closed. Over time, repeated collapse and reopening of alveoli cause inflammation, scarring (fibrosis) and thickening of the lung tissue. Some babies present with severe respiratory failure soon after birth, while others develop chronic cough, fast breathing and low oxygen later in childhood or even adulthood. The exact course depends on which gene is affected and how strong the mutation is.
Other names
Doctors and researchers may use several names for this condition. These names may sound different, but they all point to lung disease caused by long-term problems with surfactant.
Chronic respiratory distress with surfactant metabolism deficiency – the full name that stresses that the problem is long term and linked to surfactant handling.
Surfactant metabolism dysfunction (pulmonary) – a shorter term that highlights that the lung surfactant system does not work properly.
Surfactant dysfunction – a general label for any lung disease where surfactant is abnormal in amount or function.
Surfactant protein deficiency syndrome (SPDS) – often used when changes in surfactant protein genes are proven in children with interstitial lung disease.
Childhood interstitial lung disease due to surfactant dysfunction (chILD-surfactant) – used in some pediatric lung disease groups.
Types
Doctors often group this disease by which gene is affected and how the disease behaves. Different gene changes can cause similar lung problems, but age at onset and severity may differ.
SFTPB-related surfactant deficiency
Changes in the SFTPB gene lower or remove surfactant protein B (SP-B). This form usually causes very severe breathing failure in newborn babies and often needs intensive care or even lung transplant.SFTPC-related surfactant dysfunction
Changes in the SFTPC gene affect surfactant protein C (SP-C). This often causes chronic interstitial lung disease in babies, children, or adults, with long-lasting cough, fast breathing, and low oxygen rather than sudden failure at birth.ABCA3-related surfactant metabolism dysfunction
Mutations in the ABCA3 gene damage special storage bodies (lamellar bodies) that carry surfactant. This can cause severe breathing problems in newborns or chronic interstitial lung disease later in childhood.NKX2-1 (TTF-1) / other transcription factor–related forms
Some children have changes in genes such as NKX2-1 (also called TTF-1) that control lung, thyroid, and brain development. They may have lung disease plus thyroid or movement problems.Unclassified or unknown-variant surfactant metabolism deficiency
In some children, lung tissue and X-rays strongly suggest surfactant disease, but no known gene change is found. These cases are called “unclassified” and may involve new or yet-to-be-discovered genes.
Causes and risk factors
Here “cause” means anything that can directly create or strongly support this disease, or that makes it more likely in a child who already has a risky gene. Most true root causes are genetic.
SFTPB gene mutations
Harmful changes in the SFTPB gene lead to very low or absent surfactant protein B. Without enough SP-B, surfactant cannot spread well across alveoli, so the lungs collapse and become stiff, causing severe respiratory distress.SFTPC gene mutations
Some SFTPC changes make faulty SP-C protein that misfolds and injures lung cells. This injury causes long-lasting inflammation and scarring, giving a chronic interstitial lung disease picture.ABCA3 gene mutations
The ABCA3 protein moves lipids into lamellar bodies in lung cells. Mutations disturb this transport, so surfactant is poor in quality and quantity, leading to neonatal respiratory failure or chronic lung disease.NKX2-1 (TTF-1) gene mutations
NKX2-1 controls genes needed for lung and surfactant development. Variants can reduce surfactant production and also affect brain and thyroid, giving a “brain-lung-thyroid” syndrome in some children.Other rare surfactant-pathway gene variants
Newer panels sometimes find changes in genes linked to surfactant processing or immune handling of surfactant. These are less common but can still lead to chronic surfactant-related lung disease.Autosomal recessive inheritance
Some forms, especially many ABCA3 or SFTPB mutations, follow an autosomal recessive pattern. The child gets one faulty copy from each carrier parent; both are needed to cause disease.Autosomal dominant inheritance
Many SFTPC mutations act in an autosomal dominant way. A single changed gene from one parent can be enough to cause lung disease, though severity can differ within a family.De novo (new) mutations
Sometimes the gene change is new in the child and not found in either parent. This “de novo” change can still cause surfactant dysfunction and chronic respiratory distress.Family history of unexplained lung disease
Having relatives with early, unexplained lung disease, lung fibrosis, or death from respiratory failure suggests hidden surfactant gene variants as an underlying cause.Premature birth with underlying gene variants
Premature babies already have immature surfactant. If they also carry surfactant gene mutations, respiratory distress can be worse and more persistent than in typical prematurity.Age-related vulnerability in infants and children
Young lungs are still developing. When surfactant genes are abnormal, this development is disturbed, so lung scarring and chronic symptoms can begin very early in life.Consanguinity (parents related by blood)
When parents are related, there is a higher chance that both carry the same rare recessive mutation, increasing the risk that their child will inherit two faulty copies.Misfolding and toxic build-up of surfactant proteins
Some mutant surfactant proteins misfold and build up inside lung cells, causing stress and cell death. This process drives chronic inflammation and lung scarring.Abnormal lamellar body formation
ABCA3 defects disturb lamellar bodies, the storage sacs for surfactant. Poor formation of these bodies means surfactant is not packaged and released correctly into the air spaces.Abnormal surfactant lipid composition
In some children, the types of fats in surfactant are altered, which changes how well it reduces surface tension and may mark a surfactant metabolism disorder.Chronic lung inflammation as a trigger on a genetic background
Infections or other irritants may not cause the disease by themselves, but they can worsen symptoms and speed up scarring in children who already have a surfactant gene defect.Immune system imbalance against surfactant
In some interstitial lung diseases, the immune system reacts abnormally to surfactant or lung tissue. This can coexist with genetic surfactant problems and increase damage.Exposure to air pollutants or smoke in a susceptible child
Air pollution, tobacco smoke, or indoor fumes can irritate and injure lungs that already have weak surfactant, making chronic symptoms worse and lung scarring more likely.Unknown or undiscovered gene defects
Some children clearly have surfactant-type lung disease, but all known genes test normal. This suggests other genes or regulatory regions not yet discovered.Combination of several mild variants in surfactant pathways
Instead of one severe mutation, some people may have several milder changes in surfactant-related genes that together push surfactant function below a safe level.
Common symptoms
Symptoms can vary a lot. Some babies become very sick soon after birth, while other children have slower, long-term breathing problems.
Fast breathing (tachypnea)
The child breathes very quickly even at rest. This is the body’s way to try to bring in more oxygen when stiff lungs and collapsed alveoli make breathing inefficient.Shortness of breath
The child feels “out of breath” with mild activity or even during feeding. Small lungs with poor surfactant cannot move enough air in and out.Persistent dry or wet cough
A long-lasting cough, often without obvious infection, is common. It comes from irritated, inflamed airways and interstitial tissue around the air sacs.Low oxygen levels (hypoxia)
Pulse oximetry or blood gases may show low oxygen even when the child is resting. Damaged alveoli cannot transfer oxygen from air to blood properly.Bluish lips or skin (cyanosis)
When oxygen is low for a long time, the lips, tongue, or fingers can look blue or gray. This is a sign of serious oxygen lack and needs urgent medical review.Chest retractions and nasal flaring
The soft areas between ribs or at the neck sink in when the child breathes, and nostrils widen. These are signs that breathing muscles are working very hard.Crackles on lung exam
Doctors may hear fine crackling sounds over the lungs with a stethoscope. These sounds come from stiff, scarred tissue and small airways opening and closing.Finger or toe clubbing
Over time, the tips of fingers and toes may become round and bulb-shaped. This often appears in chronic lung diseases with long-term low oxygen.Poor weight gain or “failure to thrive”
Children may struggle to gain weight because breathing uses a lot of energy, feeding is tiring, and chronic illness reduces appetite.Easy tiredness with play or exercise
Older children may say they cannot keep up with friends or tire quickly when walking, running, or climbing stairs because their lungs and heart work extra hard.Frequent chest infections
Some children get repeated “pneumonia” or chest infections. Abnormal surfactant and damaged lung tissue make it harder to clear germs and mucus.Noisy breathing or wheeze
Air moving through narrowed or inflamed small airways can make whistling or squeaky sounds, especially during exhalation.Chest tightness or discomfort
Stiff lungs and increased work of breathing can feel like pressure or tightness in the chest, even in children who may not describe it clearly.Sleep disturbance from breathing problems
Some children wake up often or need oxygen at night because breathing becomes more shallow when sleeping, and low oxygen worsens.Signs of pulmonary hypertension in severe cases
Long-term low oxygen can strain the right side of the heart, leading to swelling of legs or belly and loud heart sounds, especially in advanced disease.
Diagnostic tests
Doctors do not rely on one single test. They combine history, physical exam, lung function tests, imaging, lab work, and sometimes genetic tests or lung biopsy to confirm surfactant metabolism deficiency and to rule out other causes.
Physical exam tests
Full physical exam and medical history
The doctor asks about symptoms, timing, family history, and pregnancy or birth problems. They check breathing pattern, heart rate, and overall health to see how long and how severely the lungs have been affected.Observation of breathing and chest shape
The doctor looks for fast breathing, chest retractions, nasal flaring, and chest deformities from long-term labored breathing. These clues help show chronic rather than short-term lung disease.Lung auscultation with a stethoscope
Listening over the chest can reveal crackles, decreased breath sounds, or wheeze. Fine crackles often suggest interstitial lung disease such as surfactant-related fibrosis.Growth and nutrition assessment
Measuring weight, height, and head size over time shows whether chronic lung disease is affecting growth. Poor growth supports a long-term, serious condition.
Manual tests
Spirometry (lung function test)
Older children blow into a machine that measures how much and how fast they can exhale. In interstitial lung disease, spirometry often shows a “restrictive” pattern with reduced lung volumes.Peak expiratory flow measurement
A simple handheld meter can show how fast the child can blow out air. While more often used in asthma, low values here can still support reduced lung function from chronic disease.Six-minute walk test
The child walks for six minutes while distance and oxygen levels are measured. In surfactant metabolism deficiency, oxygen may fall and the child may tire quickly, showing reduced exercise capacity.Exercise oximetry
Oxygen saturation is checked while the child moves or climbs. A drop in oxygen with activity suggests limited reserve and supports significant lung involvement.
Lab and pathological tests
Arterial blood gas (ABG)
A blood sample from an artery shows exact levels of oxygen and carbon dioxide. In this disease, oxygen is often low, especially during sleep or exercise, even when carbon dioxide is normal at first.Basic blood tests (CBC and inflammation markers)
Blood counts and markers like CRP help rule out infection, anemia, or other systemic diseases that might explain the symptoms. They are usually not specific but guide further workup.Genetic testing for surfactant genes
A blood or saliva sample is tested for changes in genes such as SFTPB, SFTPC, ABCA3, NKX2-1, and others. Finding a harmful variant can confirm surfactant metabolism deficiency and help guide family counseling.Bronchoalveolar lavage (BAL) analysis
During bronchoscopy, a small amount of fluid is flushed into the lungs and then collected. The fluid is checked for cells, proteins, and sometimes surfactant markers, to rule out infection and support a surfactant-related disorder.Lung biopsy with histopathology
In difficult cases, a small piece of lung tissue is taken and studied under a microscope. Certain patterns of scarring, cell changes, and abnormal surfactant deposits suggest genetic surfactant disease.Surfactant composition or lipid analysis (research setting)
Specialized labs can study the detailed fat and protein pattern in surfactant. Abnormal lipid profiles may point to surfactant metabolism dysfunction and can support the diagnosis in complex cases.
Electrodiagnostic / sensor-based tests
Resting pulse oximetry
A small sensor on the finger or toe measures oxygen saturation without needles. Long-term low values at rest are a simple but powerful sign of chronic lung disease.Overnight oximetry or sleep study (polysomnography)
Oxygen is monitored during sleep, sometimes with other sensors for breathing and heart rate. Drops in oxygen at night can reveal hidden severity and guide oxygen therapy.Electrocardiogram (ECG)
An ECG records the heart’s electrical activity. In advanced lung disease with pulmonary hypertension, the ECG may show strain on the right side of the heart.
Imaging tests
Chest X-ray
A simple chest X-ray may show diffuse hazy shadows, increased markings, or signs of over- or under-inflated lungs. While not specific, these findings raise suspicion for interstitial lung disease.High-resolution computed tomography (HRCT) of the chest
HRCT gives detailed images of lung structure. In surfactant disorders, it may show “ground-glass” areas, reticular lines, or cysts. These patterns help doctors suspect surfactant-related interstitial lung disease.Echocardiogram (heart ultrasound)
An ultrasound of the heart checks for high pressure in lung blood vessels (pulmonary hypertension) and heart strain. This test does not diagnose surfactant deficiency itself but shows how much the lung disease is affecting the heart.
Non-pharmacological (non-drug) treatments
Supplemental oxygen therapy
Giving extra oxygen through nasal tubes or a mask helps keep blood oxygen saturation in a safe range, reducing strain on the heart and brain. Oxygen does not fix the gene problem, but it relieves shortness of breath and improves energy and growth in children with chronic hypoxemia. Flow and duration are adjusted based on sleep and activity oxygen levels measured by pulse oximetry and blood gases.Non-invasive ventilation (NIV)
NIV uses a mask connected to a machine (CPAP or BiPAP) that gently pushes air into the lungs at set pressure. This helps keep alveoli open, improves gas exchange, reduces work of breathing and may prevent repeated hospitalizations. It is often used at night or during infections to support children who have chronic respiratory insufficiency.Invasive mechanical ventilation in intensive care
During severe crises, a breathing tube (endotracheal tube) may be needed so a ventilator can fully control breathing. Doctors use lung-protective settings with low tidal volume and adequate positive end-expiratory pressure (PEEP) to keep alveoli open and avoid more injury. This is a life-support measure used only in critical situations while other treatments are optimized.High-flow nasal cannula (HFNC)
HFNC delivers warm, humidified oxygen at high flow through soft nasal prongs. The gentle pressure helps open small airways, reduces work of breathing and improves comfort compared with a tight mask. It is often used on wards or high-dependency units for infants and children with moderate respiratory distress who do not yet need full NIV or intubation.Pulmonary rehabilitation and breathing exercises
Age-appropriate exercise programs, physiotherapy and breathing exercises improve endurance, muscle strength and airway clearance. Simple activities like walking, play-based training and controlled breathing can reduce breathlessness and improve quality of life, especially in older children and adults with chronic interstitial lung disease from surfactant dysfunction.Chest physiotherapy and airway clearance
Techniques such as percussion, vibration, postural drainage and use of oscillating devices help move mucus from small airways to larger ones where it can be coughed out. Keeping mucus moving lowers the risk of pneumonia and atelectasis (areas of lung collapse), which are common in children with chronic lung disease.Nutritional support and high-calorie feeding
Children with chronic respiratory distress burn more energy just to breathe and may fall behind in growth. Dietitians often recommend higher-calorie feeds, frequent small meals or feeding tubes (nasogastric or gastrostomy) to ensure enough calories, protein, vitamins and minerals to support lung healing, immunity and normal growth.Vaccination and infection prevention measures
Up-to-date vaccines against influenza, pneumococcus, COVID-19 and other childhood diseases are essential to avoid severe infections that can worsen lung function. Hand hygiene, avoiding tobacco smoke and reducing exposure to sick contacts are part of everyday preventive care for families caring for these children.Early and aggressive treatment of respiratory infections
When children with surfactant disorders develop cough, fever or increased breathing difficulty, doctors often start antibiotics and supportive care earlier than in healthy children. This is because even mild infections may tip them into respiratory failure, and preventing severe pneumonia is critical to protect lung tissue.Psychological and family support
Living with a chronic rare lung disease is stressful for the child and caregivers. Regular psychological support, counseling, and parent support groups help families cope with hospital stays, uncertainty and complex decisions such as considering lung transplantation. Mental health care improves overall family resilience and treatment adherence.Genetic counseling for the family
Because surfactant metabolism deficiency is often inherited, families benefit from meeting a genetic counselor. They explain carrier status, recurrence risk for future pregnancies, and options such as prenatal or pre-implantation genetic testing. This helps families make informed reproductive decisions and understand the long-term outlook.Environmental control (no smoke, low pollution)
Avoiding cigarette smoke, biomass fuel smoke and high air pollution reduces extra irritation of already sensitive lungs. Families may be advised to keep the home smoke-free, improve ventilation, use clean cooking fuels and avoid strong fumes or dust. These simple steps can lessen day-to-day symptoms and protect long-term lung function.Sleep optimization and treatment of sleep-disordered breathing
Poor sleep can worsen daytime fatigue and breathing. Some children develop sleep-related hypoventilation or obstructive events. Sleep studies help detect these problems, and nighttime oxygen or NIV can be adjusted to keep oxygen and carbon dioxide levels safe during sleep, improving growth and school performance.Physiotherapy for posture and chest expansion
Chronic disease and shortness of breath can lead to hunched posture and weak chest muscles. Physical therapists teach stretching and strengthening exercises that keep the chest wall flexible and allow better lung expansion. Good posture may reduce breathlessness during activity.Education and self-management training
As children grow older, they learn to monitor their own symptoms, use inhalers or oxygen correctly, and recognize early signs of infection or worsening distress. Education for families and teenagers builds confidence, prevents avoidable emergencies, and encourages partnership with the medical team.Home monitoring (pulse oximeter and action plans)
Some families use home pulse oximeters to check oxygen saturation during illness or sleep. Doctors provide clear action plans showing when to increase oxygen, when to call the clinic, and when to go to the emergency department. This structured plan reduces panic and improves safety at home.Rehabilitation after hospitalizations
After a long stay in intensive care, children may be weak, deconditioned and anxious. Structured rehabilitation programs, including physiotherapy, occupational therapy and psychological support, help them regain strength, function and independence. This reduces long-term disability from repeated ICU stays.Palliative care and symptom management
In severe cases where lung disease is advanced and transplant is not possible or delayed, palliative care teams help control symptoms like breathlessness, anxiety and pain. They support families with difficult decisions and focus on comfort, dignity and quality of life alongside ongoing medical care.School and social support adaptations
Children with chronic oxygen or limited exercise capacity may need modified school schedules, extra rest breaks, and help carrying oxygen equipment. Letters from the medical team and communication with teachers allow safe participation in education and social life without over-exertion.Pre-transplant evaluation and preparation
For children with severe surfactant disorders, early referral to a lung transplant center allows careful evaluation of heart, lungs, nutrition and social support. Pre-transplant rehabilitation and education improve outcomes and help families understand the risks and benefits of transplantation as a potential curative option.
Drug treatments
Important: Many of these medicines are used off-label in surfactant metabolism deficiency. Dosages vary by age, weight and other illnesses. Never start, stop or change any medicine without a specialist pulmonologist or transplant team.
Hydroxychloroquine – antimalarial / immunomodulator
Hydroxychloroquine (for example, tablets containing 200 mg hydroxychloroquine sulfate) is approved for conditions like lupus and rheumatoid arthritis but is often used off-label in children’s interstitial lung disease, including surfactant protein C or ABCA3-related disease, to reduce lung inflammation and improve oxygen needs. Typical pediatric regimens are weight-based (mg/kg/day) and require eye checks because of the risk of retinal toxicity with long-term use. Common side effects include stomach upset, skin rash and, rarely, eye or heart problems.Systemic corticosteroids (e.g., prednisone) – anti-inflammatory
Prednisone and similar steroids reduce immune-driven lung inflammation and may stabilize or improve lung function in some forms of surfactant dysfunction. Short-term higher doses may be tapered to the lowest effective maintenance dose. Long-term steroids can cause weight gain, high blood pressure, diabetes, mood changes, bone thinning and infection risk, so specialists carefully balance benefits and harms and monitor children closely.Azithromycin – macrolide antibiotic with anti-inflammatory effect
Azithromycin is approved to treat bacterial infections such as pneumonia, but low-dose, long-term regimens are sometimes used off-label to reduce airway inflammation and prevent exacerbations in interstitial lung diseases. It also covers atypical bacteria during infections. Typical pediatric doses are given once daily for a short course or three times per week chronically. Side effects include stomach upset, diarrhea, and rare heart rhythm disturbances (QT prolongation), so ECG monitoring may be needed in high-risk patients.Inhaled bronchodilators (e.g., salbutamol / albuterol) – airway smooth muscle relaxant
Short-acting beta-agonists open narrowed airways and relieve wheeze or tight chest in some patients with mixed obstructive-restrictive patterns. They are inhaled via spacer or nebulizer, often before physiotherapy or exercise. Side effects are usually mild and include tremor and fast heart rate. They do not treat the underlying surfactant defect but can ease symptoms during infections or exertion.Inhaled corticosteroids – local anti-inflammatory
Inhaled steroids like budesonide or fluticasone reduce airway inflammation with fewer systemic side effects than oral steroids. In some children with prominent airway hyper-responsiveness, they may improve cough and asthma-like symptoms. Long-term high doses can still affect growth or cause oral thrush, so mouth rinsing and lowest-effective dosing are important.Mycophenolate mofetil – immunosuppressant
Mycophenolate mofetil (CellCept) is approved to prevent rejection in kidney, heart and liver transplants and is sometimes used to treat autoimmune or chronic interstitial lung diseases. It blocks lymphocyte proliferation and can reduce immune-mediated inflammation in the lungs, especially after lung transplantation. Dosing is weight-based and divided twice daily. Side effects include low blood counts, infection risk, stomach upset and possible birth defects, so strict monitoring and contraception in older patients are necessary.Tacrolimus – calcineurin inhibitor
Tacrolimus (Prograf) is a key immunosuppressant after lung transplantation for surfactant metabolism disorders. It inhibits T-cell activation and prevents rejection of the transplanted lungs. Dosing is adjusted using blood level monitoring. Side effects include kidney damage, high blood pressure, tremor, high blood sugar and increased infection and cancer risk, so it is used only under experienced transplant teams.Cyclosporine – calcineurin inhibitor
Cyclosporine is another calcineurin inhibitor used with mycophenolate and steroids in transplant immunosuppression. It helps maintain graft function by suppressing T-cell activity. Doses are titrated by blood levels. Side effects include kidney impairment, high blood pressure, gum overgrowth, increased hair growth and infection risk, requiring regular lab checks and dose adjustments.Trimethoprim–sulfamethoxazole (TMP-SMX) – infection prophylaxis
Children on long-term steroids or immunosuppressants often receive low-dose TMP-SMX to prevent Pneumocystis jirovecii pneumonia, a serious opportunistic infection. Dosing is usually based on trimethoprim mg/kg several days per week. Side effects can include rash, bone-marrow suppression and allergy, so blood counts are checked regularly.Loop diuretics (e.g., furosemide) – fluid management
If chronic hypoxemia and pulmonary hypertension strain the heart, children may develop fluid overload. Furosemide helps remove excess fluid, reducing lung congestion and breathlessness. It is given orally or intravenously in mg/kg doses. Long-term use may disturb electrolytes and affect kidney function, so it is monitored carefully.ACE inhibitors or pulmonary hypertension drugs
In some patients, high pressure in lung blood vessels (pulmonary hypertension) develops. Medicines like ACE inhibitors or specific pulmonary vasodilators (for example sildenafil or bosentan) may be used to reduce pressure and improve right-heart function. These drugs need careful titration and monitoring for liver, blood pressure and other side effects.Proton-pump inhibitors (PPIs)
Reflux of stomach acid into the esophagus and airways can worsen lung injury. PPIs reduce gastric acid production and may protect lungs from micro-aspiration. They are often used when reflux symptoms or aspiration are suspected. Side effects include altered mineral absorption and infection risk with long-term high-dose use.Palivizumab (RSV monoclonal antibody)
For high-risk infants with chronic lung disease, monthly palivizumab injections during RSV season can lower the risk of severe respiratory syncytial virus infection. Although it does not affect the genetic defect, preventing RSV is crucial because these infections can cause life-threatening decompensation. Side effects are usually mild injection-site reactions.Broad-spectrum intravenous antibiotics
During severe pneumonias or after transplant, broad-spectrum antibiotics are used to treat bacterial infections quickly. The choice is based on local resistance patterns and culture results. Doses and combinations are adjusted by weight and kidney function. Overuse can cause resistance, gut flora changes and drug toxicity, so stewardship is important.Antifungal agents
Immunosuppressed patients after transplant are at high risk of fungal infections such as aspergillosis. Prophylactic or therapeutic antifungals (e.g., voriconazole) may be used. These drugs have important interactions with calcineurin inhibitors and can affect liver function, so levels and labs must be monitored closely.Antiviral prophylaxis
Drugs such as valganciclovir may be prescribed after transplant to prevent cytomegalovirus (CMV) and other viral infections that threaten graft survival. They are weight-based and time-limited. Side effects like bone-marrow suppression require regular blood tests.Vitamin D and calcium supplements
Long-term steroids and limited sun exposure increase risk of weak bones. Vitamin D and calcium support bone health and reduce fracture risk. Doses are age- and level-based. Excess intake can cause high calcium levels, so supplementation follows blood level monitoring and expert advice.Iron and erythropoiesis-stimulating agents (when needed)
Chronic disease and frequent blood tests can cause anemia, worsening breathlessness. Iron supplements or, in some cases, erythropoiesis-stimulating agents may help improve red blood cell levels, but they are only used after identifying the cause of anemia and are carefully monitored to avoid high hemoglobin or clotting risk.Analgesics and anxiolytics (careful use)
Low-dose pain or anxiety medicines may be used in hospital or palliative care to relieve severe breathlessness and distress. Doses are titrated gently to avoid suppressing breathing. Psychological therapies are always combined so that medicines are not the only support.Experimental targeted therapies (research setting only)
New research explores gene-specific and molecular treatments targeting particular surfactant mutations or protein processing pathways, but these are still experimental. They are only given in clinical trials with strict safety monitoring and are not part of routine care yet.
Dietary molecular supplements
Supplements should never replace prescribed treatment. Always check with the medical team before starting any supplement to avoid interactions.
Omega-3 fatty acids – may have mild anti-inflammatory effects and support heart and brain health.
Vitamin D – supports bone health and immune function, especially important in children on steroids.
Antioxidant vitamins (C and E) – might help neutralize oxidative stress in chronic lung inflammation.
Zinc – supports immune responses and wound healing; deficiency is common in chronically ill children.
Selenium – cofactor for antioxidant enzymes; low levels may worsen oxidative lung injury.
Probiotics – support gut microbiome, which may indirectly influence immunity and inflammation.
High-energy oral nutrition formulas – provide concentrated calories and protein for growth.
Whey or casein protein supplements – help preserve muscle mass in children who tire easily and eat less.
Multivitamin–mineral preparations – cover general micronutrient needs when diet is limited by breathlessness.
Specialized pediatric nutrition (tube feed formulas) – balanced formulas given via feeding tube when oral intake is not enough, ensuring adequate calories, protein, vitamins and trace elements.
Immune-supporting, regenerative and stem-cell related therapies
Standard childhood vaccinations
Timely vaccines are the safest, most evidence-based way to support immunity. They protect against infections that can be life-threatening in children with surfactant disorders and on immunosuppression.RSV monoclonal antibody (palivizumab)
As discussed, palivizumab boosts passive immunity against RSV during high-risk seasons in selected infants and reduces hospitalization risk.Nutritional and vitamin optimization
Ensuring adequate calories, protein, vitamin D, zinc and other micronutrients keeps the immune system strong and better able to fight infections.Hematopoietic or mesenchymal stem cell therapies (experimental)
At present, stem cell therapies for surfactant metabolism deficiency are experimental and limited to research. No stem cell drug is widely approved to regenerate lung tissue in this condition, and unregulated “stem cell clinics” can be dangerous. Families should only consider such options within established clinical trials.Lung transplantation as a functional “regenerative” therapy
Lung transplantation replaces diseased lungs with donor lungs that have normal surfactant-producing cells. It does not change the patient’s genes, but it effectively restores lung function and can provide long-term survival for carefully selected children.Future gene-based therapies (research)
Scientists are working on gene-editing and gene-replacement strategies for surfactant gene mutations. These approaches aim to correct the root cause but are still in early research phases. Families should be cautious of unproven “gene cures” advertised outside regulated trials.
Surgical and interventional treatments
Lung biopsy (surgical or thoracoscopic)
Doctors sometimes need a small piece of lung tissue to confirm the diagnosis and exclude other diseases. Through keyhole surgery (VATS) or a small incision, a tiny wedge of lung is removed and examined under the microscope and by genetic tests. This helps guide long-term treatment decisions.Tracheostomy
In children who need very long-term mechanical ventilation, a tracheostomy (breathing tube in the neck) may be placed. It can improve comfort, allow speech with special valves, and make home ventilation more practical, but it requires meticulous daily care to prevent infection and blockage.Gastrostomy tube placement
For children who cannot eat enough because of breathlessness or who aspirate food, a feeding tube directly into the stomach (PEG or surgical gastrostomy) allows safe, reliable nutrition and medication delivery. This supports growth and strength, which are vital before transplant or during chronic illness.Lung transplantation
Double-lung transplantation is the main surgical cure for severe surfactant metabolism deficiency. After careful evaluation, both diseased lungs are removed and replaced with donor lungs. Survival at 1 year in children transplanted for surfactant disorders can be good, and 5-year survival is similar to other pediatric lung transplant indications, but lifelong immunosuppression is required.Pre- or post-transplant interventions (e.g., bronchoscopy, stenting)
After transplant, bronchoscopies are used to inspect the airways, take biopsies for rejection or infection, and sometimes place stents if airways narrow. These minimally invasive procedures help maintain graft health and detect problems early.
Prevention and lifestyle measures
Keep the home completely smoke-free.
Follow all vaccination schedules and any extra vaccines recommended by the specialist.
Practice strict hand hygiene and avoid crowded places during major viral seasons when possible.
Maintain good nutrition with enough calories and protein to support growth.
Ensure regular follow-up with pediatric pulmonology and genetics clinics.
Use oxygen, inhalers and devices exactly as prescribed and keep equipment well maintained.
Recognize early signs of infection (fever, more cough, faster breathing) and seek medical advice promptly.
Encourage gentle physical activity within the child’s limits to keep muscles strong.
Protect against extreme cold or very polluted air by using masks or staying indoors when necessary.
Plan for transition of care as the child grows into adulthood, so expertise continues in adult rare-lung-disease clinics.
When to see doctors urgently
Families should seek urgent medical help or emergency care if the child has any of these warning signs: breathing much faster than usual, struggling to speak, bluish lips or face, chest pulling in between the ribs, new or high fever, sudden drop in oxygen saturation compared with baseline, unusual sleepiness, confusion, or if home oxygen and usual rescue measures do not relieve symptoms. Any sudden worsening after transplant, such as sharp chest pain, severe breathlessness or drop in lung function, also needs immediate assessment for rejection or infection. When in doubt, it is safer to go to the emergency department than to wait at home.
What to eat and what to avoid
Eat: small, frequent, high-calorie meals and snacks to reduce tiredness while eating.
Eat: foods rich in protein such as eggs, fish, lean meat, beans and dairy to support muscle and lung repair.
Eat: fruits and vegetables for vitamins, minerals and antioxidants, adjusted for the child’s appetite.
Eat: healthy fats like olive oil, nut butters and avocado to add calories without large volume.
Drink: enough fluids to keep mucus thinner, unless restricted for heart or kidney reasons.
Avoid: very large, heavy meals that can push up the diaphragm and make breathing harder.
Avoid: highly salty processed foods if the child has heart strain or fluid issues.
Avoid: energy drinks and high-caffeine beverages in older children, which may worsen heart rhythm issues, especially if on certain medicines.
Avoid: herbal or over-the-counter supplements without checking with the specialist, because of possible drug interactions.
Adapt: texture and timing of meals (for example, soft foods after tiring physiotherapy sessions) to reduce fatigue and aspiration risk.
Frequently asked questions (FAQs)
Is surfactant metabolism deficiency always genetic?
Most cases are linked to mutations in surfactant genes like SFTPB, SFTPC, ABCA3 or NKX2-1, but sometimes no mutation is found even though the clinical picture fits. Ongoing research continues to discover new genes and mechanisms.Can children with this condition live into adulthood?
Yes. Some children with milder mutations have chronic but stable disease and reach adulthood with supportive care. Others with severe defects may need lung transplantation in childhood. Prognosis varies widely and is best discussed with the specialist team.Is there a cure without transplant?
For most known genetic surfactant deficiencies, there is currently no approved medicine that completely corrects the defect. Medicines like hydroxychloroquine and steroids may improve symptoms and slow progression in some patients, but the only established curative procedure for severe forms is lung transplantation.Why is hydroxychloroquine used if it is not approved specifically for this disease?
Studies and case reports suggest that hydroxychloroquine can improve lung function and oxygen needs in some children with SP-C or ABCA3-related interstitial lung disease by modulating immune and cellular pathways, so doctors may use it off-label when potential benefits outweigh risks.How is the diagnosis confirmed?
Diagnosis usually combines clinical findings, high-resolution CT scans, sometimes lung biopsy, and genetic testing of known surfactant genes. Genetic confirmation helps guide prognosis, family counseling and, in some cases, targeted trial therapies.Will all siblings have the same disease?
Many forms are autosomal recessive, meaning both parents carry one faulty gene. Each pregnancy has a 25% chance of an affected child, 50% chance of a carrier and 25% chance of a non-carrier. Genetic counseling explains the pattern for each family.Does surfactant replacement therapy cure the disease?
In newborns with respiratory distress syndrome from prematurity, surfactant replacement works very well. In inherited surfactant metabolism deficiency, surfactant replacement may give short-term improvement but does not fix the underlying production problem, so benefits are limited and temporary.What are the main risks of lung transplantation?
Major risks include surgical complications, acute and chronic rejection, infection, kidney damage from immunosuppressants, and increased risk of certain cancers. Despite these, many children gain years of improved breathing and better quality of life after transplant.Can lifestyle changes alone control the disease?
Healthy lifestyle, good nutrition and infection prevention are essential, but by themselves they cannot correct the genetic defect or fully stop lung damage. They must always be combined with medical and sometimes surgical treatments guided by specialists.Is exercise safe for a child with this condition?
Usually yes, within limits set by the medical team. Light to moderate activity, sometimes with oxygen, helps maintain strength and mood. The doctor may recommend supervised pulmonary rehabilitation to find a safe level for each child.Can this disease return after lung transplantation?
Because the defect is in the patient’s genes but the new lungs come from a healthy donor, the same surfactant deficiency does not typically recur in the transplanted lungs. However, other problems like rejection or infection can still damage the graft.Are gene therapies available now?
At present, gene therapies for surfactant metabolism deficiency are still experimental and not available as routine care. Clinical trials may open in the future, and families should rely on information from recognized academic centers, not unregulated clinics.Does every patient need a lung biopsy?
No. If genetic testing plus clinical and imaging findings are clear, a biopsy may not be necessary. Biopsy is reserved for cases where the diagnosis remains uncertain or where results would change management.How often should follow-up visits occur?
Frequency depends on disease severity. Infants and children with unstable disease may need monthly or even more frequent reviews, while stable older patients may be seen every few months. After transplant, visits are more frequent to monitor rejection and drug levels.What is the most important message for families?
Although surfactant metabolism deficiency is serious and sometimes life-threatening, early diagnosis, expert multidisciplinary care, good home management and, when needed, lung transplantation can provide meaningful years of life. Families are not alone; rare-disease networks and support groups can share experience, information and hope.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 25, 2025.
