Alveolar capillary dysplasia

Rare lung disease, present at birth and treatable by lung transplants

Alveolar capillary dysplasia
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Synonyms	Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV)
Pronounce
Field	Pediatric pulmonology, neonatology, medical genetics
Symptoms	Cyanosis (blue lips or skin), tachypnea (rapid breathing), hypoxemia, respiratory distress, poor feeding, failure to respond to oxygen therapy
Complications	Respiratory failure, hypoxia, multiorgan dysfunction, death
Onset	Typically within the first 24 to 48 hours after birth
Duration	Rapidly progressive without intervention
Types	Classic (early-onset), atypical (late or focal onset)
Causes	Mutation or deletion involving the FOXF1 gene or regulatory region
Risks	Sporadic mutation; rare familial cases; possible association with other congenital anomalies (especially cardiac, gastrointestinal, and urogenital malformations)
Diagnosis	Clinical presentation, lung biopsy, genetic testing for FOXF1 mutations
Differential diagnosis	Persistent pulmonary hypertension of the newborn (PPHN), sepsis, pneumonia, surfactant deficiencies, hyaline membrane disease, pulmonary hypoplasia, acinar dysplasia, congenital alveolar dysplasia
Prevention	None currently known
Treatment	Supportive care, extracorporeal membrane oxygenation (ECMO), lung transplant (only definitive treatment)
Medication	Pulmonary vasodilators (e.g., inhaled nitric oxide, sildenafil), inotropic support, mechanical ventilation
Prognosis	Poor; extremely high mortality rate in the neonatal period without lung transplant
Frequency	Rare; exact incidence unknown
Deaths	Nearly universal without transplant in severe cases

Alveolar capillary dysplasia (ACD) is a rare and serious congenital disorder characterized by the abnormal development of the capillary vascular system within the lungs. This condition leads to severe pulmonary hypertension and respiratory distress in newborns, often resulting in early neonatal death.

Pathophysiology

Alveolar capillary dysplasia is primarily a developmental disorder of the pulmonary vasculature. In normal lung development, the alveoli are closely associated with a rich network of capillaries, facilitating efficient gas exchange. In ACD, there is a malformation of the capillary bed, where the capillaries are either absent or improperly aligned with the alveoli. This misalignment prevents adequate oxygenation of the blood, leading to hypoxemia and respiratory failure.

Genetics

ACD is often associated with genetic mutations, particularly in the FOXF1 gene located on chromosome 16. Mutations in this gene disrupt normal lung development, leading to the characteristic features of ACD. The condition can occur sporadically or be inherited in an autosomal dominant pattern, although familial cases are rare.

Clinical Presentation

Newborns with alveolar capillary dysplasia typically present with severe respiratory distress shortly after birth. Symptoms include rapid breathing (tachypnea), cyanosis, and difficulty maintaining adequate oxygen levels despite supplemental oxygen therapy. The condition is often resistant to conventional treatments for pulmonary hypertension.

Diagnosis

The diagnosis of ACD is challenging and often requires a high index of suspicion. It is typically confirmed through a combination of clinical presentation, imaging studies, and histopathological examination of lung tissue. A lung biopsy revealing the characteristic absence or misalignment of capillaries is definitive for diagnosis. Genetic testing can also identify mutations in the FOXF1 gene, supporting the diagnosis.

Management

There is currently no cure for alveolar capillary dysplasia, and management is primarily supportive. Treatment focuses on alleviating symptoms and may include mechanical ventilation, administration of nitric oxide to reduce pulmonary hypertension, and extracorporeal membrane oxygenation (ECMO) in severe cases. Lung transplantation has been considered in some cases, but the rarity and severity of the condition make it a challenging option.

Prognosis

The prognosis for infants with ACD is generally poor, with most affected newborns succumbing to the condition within the first few weeks of life. Early diagnosis and supportive care can improve outcomes, but the overall survival rate remains low.

Related pages

• Pulmonary hypertension
• Respiratory distress syndrome
• Congenital disorders
• Genetic mutations

NIH genetic and rare disease info

• NIH info on Alveolar capillary dysplasia

Alveolar capillary dysplasia is a rare disease.