Alveolar capillary dysplasia
Alveolar capillary dysplasia | |
---|---|
Other names | Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) |
congenital alveolar dysplasia[1] | |
Prevention | None[1] |
Treatment | Lung transplant[1] |
Medication | Pulmonary vasodilators |
Prognosis | Mortality rate ~100%[1] |
Frequency | Unknown[1] |
Alveolar capillary dysplasia (ACD) is a rare,
Most cases of ACD are caused by mutations affecting the gene FOXF1 or its nearby enhancer region.[3] Exactly how these mutations lead to abnormal lung development is unknown. Abnormal lung development is characterized by thickened alveolar interstitium, misplacement of pulmonary capillaries away from the alveolar surface, and fewer capillaries overall. This results in poor gas exchange and pulmonary hypertension.[1] There is evidence for connections between pulmonary arteries and systemic vessels, which would additionally contribute to poor blood oxygenation.[4]
ACD is typically diagnosed by examination of lung tissue under a
ACD is a rare disease. About 100 cases have been reported.[1] The first case was reported in 1981.[5]
Signs and symptoms
ACD is a congenital disease whose symptoms appear within hours to days after birth. Babies with ACD usually have no symptoms at the time of birth, but soon after will begin to breathe rapidly, showing increased work of breathing, and may have blue discoloration around the lips, arms, or legs, especially when feeding or crying. If an
Atypical forms of ACD have been reported with only mildly rapid breathing shortly after birth. They may present with the above symptoms of ACD at several months of age. Their symptoms may improve with standard pulmonary hypertension therapies for weeks to months before symptoms return.[1]
Babies born with ACD usually have other congenital abnormalities affecting the
Cause
Most cases of ACD are caused by
Mechanism
How mutations affecting FOXF1 or its regulatory region cause ACD is unknown. ACD-causing mutations result in abnormal development of lung vasculature and alveoli. In ACD, the interstitium of alveoli is thickened, with few to no
Another characteristic histologic finding is the presence of a pulmonary vein located next to a pulmonary artery and bronchus in the same bronchovascular bundle. In a normal lung, the pulmonary vein courses with lymphatic vessels in the lung septa.[citation needed]
Diagnosis
The gold standard for ACD diagnosis is by examination of lung tissue under a microscope. The diagnosis is made if the pathologist sees the characteristic findings of ACD: misplaced pulmonary veins adjacent to pulmonary arteries, abnormal alveoli with thickened interstitia and abnormal capillary development. Due to the rapidly progressive course of ACD, this diagnosis is frequently made during autopsy. If ACD is suspected early, examination of tissue from lung biopsy results in the quickest diagnosis.[1] Genetic testing for FOXF1 is now available and can allow for slower but non-invasive diagnosis. As not all disease-causing mutations are known, false negatives or results of uncertain significance are possible with genetic testing.[2]
There are no characteristic pattern of routine lab results or imaging findings that allow definitive diagnosis of ACD.[1]
Treatment
Initial treatments attempt to improve low blood oxygenation and high pulmonary blood pressures. Because blood oxygen content is usually very low, babies with ACD are often
For infants with atypical ACD who initially had milder symptoms and present at months of life, there can be better response to therapy. There have been reports of infants with ACD surviving to 20 or 36 months without lung transplantation. Bilateral lung transplantation may be the definitive treatment.[citation needed]
Epidemiology
ACD is a rare disease. As of 2011, about 100 cases had been reported. It is likely an under-recognized cause of death shortly after birth because diagnosis requires microscopic examination of lung tissue or specialized genetic testing, or death can be attributed to severe heart or intestinal congenital abnormalities which frequently occur in ACD.[1]