Pulmonary Alveolar Microlithiasis
Disease Details
Family Health Simplified
- Description
- Pulmonary alveolar microlithiasis is a rare lung disease characterized by the accumulation of tiny calcium phosphate stones within the alveoli.
- Type
- Pulmonary alveolar microlithiasis is a rare lung disease. The type of genetic transmission for this condition is autosomal recessive.
- Signs And Symptoms
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Patients typically have no symptoms until the third or fourth decade of life. In most cases, the disease is discovered incidentally on routine chest Xray. The most common symptoms include the following:
dyspnea
dry cough
chest pain
sporadic hemoptysis
asthenia
pneumothoraces - Prognosis
- Pulmonary alveolar microlithiasis (PAM) is a rare lung disease characterized by the accumulation of tiny calcium phosphate microliths within the alveoli. The prognosis for PAM is variable and largely depends on the rate of disease progression. While some individuals remain asymptomatic for many years, others may experience a gradual decline in lung function, leading to respiratory failure. There is currently no effective treatment for PAM, and management primarily focuses on supportive care. Lung transplantation may be considered in severe cases.
- Onset
- Pulmonary alveolar microlithiasis typically has an insidious onset, often beginning in late childhood or early adulthood. Many patients remain asymptomatic for years, with symptoms usually appearing between the ages of 20 and 40.
- Prevalence
- Pulmonary alveolar microlithiasis is an extremely rare genetic lung disorder with an estimated prevalence of less than 1 case per million people globally.
- Epidemiology
- Since the disease was first described in 1918, over 500 case reports have appeared in the literature. PAM is associated with consanguinity. The incidence is higher in Turkey, Japan, India and Italy. The disease affects both men and women equally, and it has been associated with intermarriage within families. The mean age at diagnosis is 35 years based on the cases reported in the literature.
- Intractability
- Pulmonary alveolar microlithiasis (PAM) is generally considered intractable because there is no specific, effective treatment available that can reverse or significantly improve the disease. The condition is characterized by the accumulation of calcium phosphate microliths within the alveoli of the lungs. Management primarily focuses on monitoring and supportive care, such as oxygen therapy, but lung transplantation may be considered in advanced cases.
- Disease Severity
- Pulmonary alveolar microlithiasis (PAM) varies in severity among patients. It can be asymptomatic in some individuals, detected incidentally via imaging. However, it can progress to cause respiratory symptoms such as cough, dyspnea, and in advanced cases, respiratory failure. The rate of progression and severity are highly variable.
- Healthcare Professionals
- Disease Ontology ID - DOID:12117
- Pathophysiology
- Pulmonary alveolar microlithiasis (PAM) is a rare lung disease characterized by the formation of tiny calcium phosphate microliths within the alveoli. The exact pathophysiology is not fully understood, but it is often linked to mutations in the SLC34A2 gene, which encodes a type IIb sodium-phosphate cotransporter enzyme expressed in alveolar type II cells. This mutation causes impaired phosphate transport and extrusion, leading to phosphate accumulation and subsequent microlith formation within the alveoli. The condition is usually inherited in an autosomal recessive manner. The gradual accumulation of microliths results in progressive respiratory issues, including dyspnea and reduced lung function over time.
- Carrier Status
- Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive disorder. Carrier status for PAM means an individual has one copy of the mutated SLC34A2 gene, but typically does not exhibit symptoms of the disease. Carriers can pass the gene mutation to their offspring. If two carriers have a child, there is a 25% chance the child will have PAM, a 50% chance the child will be a carrier, and a 25% chance the child will have neither gene mutation.
- Mechanism
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Pulmonary alveolar microlithiasis (PAM) is a rare lung disease characterized by the widespread presence of tiny calcium phosphate stones, known as microliths, within the alveoli, the tiny air sacs in the lungs.
**Mechanism:**
The condition is primarily caused by a mutation in the SLC34A2 gene, which encodes a sodium-phosphate cotransporter (NaPi-IIb) responsible for the phosphate transport in the lungs. This mutation leads to defective phosphate homeostasis in the alveoli, promoting the formation of microliths.
**Molecular Mechanisms:**
1. **Gene Mutation (SLC34A2):** Mutations in the SLC34A2 gene result in a dysfunctional NaPi-IIb transporter, reducing the ability to clear phosphate from alveolar epithelial cells.
2. **Phosphate Accumulation:** The impaired phosphate transport causes an accumulation of phosphate in the alveolar space, which then combines with calcium to form calcium phosphate microliths.
3. **Deposition of Microliths:** The microliths accumulate over time within the alveoli, leading to the progressive stiffening and dysfunction of the lung tissue.
These molecular mechanisms collectively result in the gradual deterioration of lung function, often leading to respiratory complications in affected individuals. - Treatment
- To date, no treatment has been proven to reverse or prevent the progression of PAM effectively. Lung transplantation is an option for the end-stage disease but is typically only recommended as a last resort when the quality of life is significantly impaired.Although no effective treatment exists, there are several common supportive care approaches that can alleviate symptoms resulting from PAM. Domiciliary oxygen should be prescribed to the patient for hypoxemia to prevent manifest desaturation.Etidronate is a bisphosphonate and can reduce the formation of calcium hydroxyapatite crystals. It has led to clinical and radiological improvements in few cases.Smoking should be prohibited for patients to avoid exacerbating disease progression.
- Compassionate Use Treatment
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Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by the deposition of microscopic calcium phosphate crystals within the alveoli of the lungs. There are no well-established treatments approved specifically for PAM, but some off-label and experimental treatments have been explored:
1. **Ertugliflozin**: This SGLT2 inhibitor, primarily used to manage diabetes, has been suggested in some studies for PAM due to its potential to reduce phosphate levels within the body, thereby possibly mitigating crystal deposition.
2. **Bisphosphonates**: Medications like etidronate, typically used to treat bone diseases, have been considered for their potential to inhibit calcium phosphate crystal formation.
3. **Corticosteroids**: While long-term efficacy is not well-documented, corticosteroids may be used in some cases to reduce inflammation and manage symptoms.
4. **Lung Transplantation**: In advanced cases where respiratory function is severely compromised, lung transplantation may be considered as a treatment option.
Given the rarity of PAM, patients are often included in compassionate use programs or clinical trials to access emerging therapies. - Lifestyle Recommendations
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For pulmonary alveolar microlithiasis (PAM), a rare lung disease characterized by the accumulation of tiny calcium phosphate microliths within the alveoli, lifestyle recommendations can help manage symptoms and improve quality of life:
1. **Avoid Smoking**: Smoking can exacerbate lung disease and worsen respiratory symptoms.
2. **Stay Hydrated**: Drinking plenty of fluids can help thin mucus and make it easier to expel.
3. **Healthy Diet**: A balanced diet can support overall health and immune function.
4. **Regular Exercise**: Moderate exercise can help maintain lung function and overall fitness, but it should be tailored to individual capacity and tolerance.
5. **Monitor Environmental Exposures**: Avoid exposure to pollutants, dust, and other respiratory irritants.
6. **Vaccinations**: Stay updated on vaccinations, especially annual flu shots and pneumococcal vaccines, to prevent respiratory infections.
7. **Regular Medical Check-ups**: Maintain regular follow-ups with healthcare providers to monitor lung function and manage symptoms effectively.
For specific concerns and personalized recommendations, consulting with a healthcare professional is essential. - Medication
- Pulmonary alveolar microlithiasis is a rare lung disease characterized by the accumulation of tiny calcium phosphate stones in the alveoli. Currently, there is no specific or curative medication available for this condition. Treatment is mainly supportive and focused on managing symptoms and complications. In advanced cases, lung transplantation may be considered. Research is ongoing to find effective treatments.
- Repurposable Drugs
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Pulmonary alveolar microlithiasis is a rare lung disease characterized by the accumulation of tiny calcium phosphate stones within the alveoli. Given its rarity, there is limited information on repurposable drugs specifically approved for this condition. However, some case reports and small studies have suggested potential benefits from drugs traditionally used for other conditions.
1. **Bisphosphonates (e.g., disodium etidronate and alendronate)**: These drugs, commonly used for osteoporosis, may have a role due to their ability to inhibit calcium phosphate deposition.
2. **Corticosteroids**: In some cases, corticosteroids like prednisone have been tried to reduce inflammation, although evidence supporting their effectiveness is limited.
3. **Colchicine**: Typically used to treat gout, colchicine may reduce inflammation and has been considered in some experimental treatments.
Further research is necessary to establish the efficacy and safety of these drugs in treating pulmonary alveolar microlithiasis. Always consult a healthcare professional before considering any treatment options. - Metabolites
- In pulmonary alveolar microlithiasis, the primary abnormality lies in the deposition of tiny calcium phosphate microliths within the alveoli. The role of metabolites specifically associated with this condition is not well-defined. However, one significant aspect is the potential disruption of surfactant metabolism and the possible involvement of mutations in the SLC34A2 gene, which encodes a sodium-phosphate cotransporter responsible for phosphate homeostasis. This disruption can lead to phosphate accumulation and subsequent microlith formation.
- Nutraceuticals
- There are currently no specific nutraceuticals proven to be effective for treating pulmonary alveolar microlithiasis (PAM). PAM is a rare lung disease characterized by the deposition of small calcium phosphate microliths within the alveoli. The management of PAM primarily focuses on monitoring the disease progression and, in severe cases, considering lung transplantation. Nutritional supplements or other nutraceuticals have not been demonstrated to alter the course of the condition. Always consult healthcare professionals for tailored medical advice.
- Peptides
- Pulmonary alveolar microlithiasis (PAM) is a rare lung disease characterized by the accumulation of calcium phosphate microliths within the alveoli. There is no established treatment involving peptides or nanotechnology specifically for PAM. Research is ongoing to better understand the disease and potential therapeutic approaches. Current management mainly involves supportive care and monitoring, with lung transplantation being an option in advanced cases.