Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The rare disease that we will be learning about today is:

Alveolar Capillary Dysplasia

Sometimes called alveolar capillary dysplasia with misalignment of pulmonary veins.

What is Alveolar Capillary Dysplasia?

• Alveolar capillary dysplasia (ACD) is a rare genetic lung disease in which the lungs are affected by abnormal blood vessels, leading to symptoms
  • These unusual blood vessels are unable to oxygenate and remove CO2 from the blood and cause very high pulmonary blood pressure
• Symptoms often begin soon after birth
• Often, alveolar capillary dysplasia leads to rapid-onset respiratory failure and is fatal in most cases
• However, less severe cases have been reported
• A little over 100 cases have been recorded
• Due to the complex diagnostic process and frequent presence of other complications, this disease may be an underreported cause of early death shortly after birth

How Do You Get It?

• Alveolar capillary dysplasia is linked to point and deletion mutations impacting the gene FOXF1
  • This gene is found on chromosome 16
  • Scientists aren’t sure how this mutation causes ACD, but it results in abnormal development of the lung alveoli and blood vessels
• This disorder is inherited in an autosomal dominant pattern, meaning that only one mutated copy of the gene needs to be inherited in order to cause the disease
• Research appears to indicate that the FOXF1 regulatory region is imprinted, meaning that some people may carry the mutation without few to no symptoms

What Are the Symptoms?

• Typically, symptoms begin with hours following birth
• Symptoms can include:
  • Rapid, labored breathing, which is often the first symptom
    • In abnormal cases, only mild rapid breathing may be present
  • Blue discoloration, which can occur around the lips or limbs
  • Thickened right ventricle
• Often, babies born with alveolar capillary dysplasia also have abnormalities affecting other organs, such as the urinary system, heart, genitalia, and intestines

How Is It Treated?

• For severe disease, there are no effective therapies
• Babies diagnosed with the disease are almost immediately sedated, intubated, and placed on mechanical ventilation. Often, pure oxygen is used due to the very low levels of oxygen in the blood
• Inhaled nitric oxide or sildenafil, a vasodilator, are used to reduce pulmonary blood pressure.
• Unfortunately, for many patients, these measures only offer temporary relief from symptoms.
• For the smaller subset of patients that present with milder symptoms after a few months of lifespan, these treatments can be more effective
  • However, even these patients can only survive for at most three years unless they receive a double lung transplant, which may be the only definitive treatment.

Where Can I Learn More???

• Learn more about this disease from the Alveolar Capillary Dysplasia Association.
• Check out our cornerstone on this disease here.