What are the other Names for this Condition? (Also known as/Synonyms)

• CDG-1a (Congenital Disorder of Glycosylation Type 1a)
• Congenital Disorder of Glycosylation Type 1a (CDG-1a)
• COPA-Associated Autoinflammatory Disease

What is COPA Syndrome? (Definition/Background Information)

• COPA Syndrome is a rare genetic disorder caused by mutations in the COPA gene that affects the way sugars are attached to proteins in the body. This leads to abnormal functioning of various organs and systems, including the lungs, kidneys, and joints
• COPA Syndrome is named after the COPα (COPalpha) protein produced by the COPA gene. It is caused by mutations in the COPA gene and inherited in an autosomal dominant pattern. Risk factors include a positive family history of the disorder and inheriting one copy of the mutated COPA gene from either parent
• The signs and symptoms of COPA Syndrome are related to various forms of lung disease, arthritis, and renal disease. Generally, all affected individuals have lung disease, about 50% present arthritis, and fewer may develop kidney disease. 
• The syndrome is also known as Congenital Disorder of Glycosylation Type 1a (CDG-1a), with symptom onset generally noted during infancy or early childhood. It is typically diagnosed based on a combination of clinical examination, laboratory tests, imaging studies, and genetic testing
• The treatment of COPA Syndrome is typically symptomatic and supportive and may include antibiotics to prevent and treat infections and medications to manage any additional symptoms. Individuals with severe lung or kidney disease may need organ transplantation
• Currently, there are no available measures to prevent COPA Syndrome as it is a genetic condition. Genetic counseling and testing may be recommended for individuals with a family history of the disorder and couples planning to have children
• The prognosis varies depending on the severity of the disorder and the effectiveness of the treatment. With appropriate treatment, most individuals with COPA Syndrome can have an improved quality of life. However, without suitable treatment, the disorder can result in severe functional limitations and complications

Who gets COPA Syndrome? (Age and Sex Distribution)

• COPA Syndrome is an extremely rare disorder with a congenital manifestation
• The syndrome is most often diagnosed during childhood, from about five years old onward. About 10% of the cases are diagnosed in adulthood
• It affects both males and females, but a predilection for females is noted
• As of 2020, fewer than 60 cases have been described. However, since it is a complex disease to diagnose, the number of cases reported may be much higher than recorded

What are the Risk Factors for COPA Syndrome? (Predisposing Factors)

The risk factors for COPA Syndrome include:

• Having a family history of the disorder
• Inheriting one copy of the mutated COPA gene from a parent to develop the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of COPA Syndrome? (Etiology)

COPA Syndrome is a genetic disorder caused by mutations in the COPA gene. It leads to abnormal functioning of various organs and systems, including the lungs, joints, and kidneys.

• The syndrome is caused by mutations in the COPA gene and is inherited in an autosomal dominant manner, with variable expressions between patients, even within families
• Sometimes, a new mutation may cause COPA Syndrome in individuals without a family history of the disorder. Therefore, spontaneous mutations may occur in individuals having both parents with normal COPA genes

Autosomal dominant mode of inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly functioning gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of COPA Syndrome?

The common signs and symptoms of COPA Syndrome occur from the involvement of the lungs, joints, and kidneys. This results in:

• Shortness of breath, cough, rapid breathing, coughing up blood, and low oxygen level (commonly noted) 
• Blood in urine
• Kidney cysts, kidney stones, and kidney infections
• Tender, swollen, and stiff joints
• Gastroesophageal reflux disease (GERD)
• Cysts may form in the lungs

The onset of COPA Syndrome is usually observed in early childhood. The disorder has variable expressivity, and therefore the findings and severity of the disorder may vary, even among close family members.

How is COPA Syndrome Diagnosed?

COPA Syndrome is typically diagnosed based on a combination of the following:

• Clinical examination and assessment of presenting signs and symptoms
• Evaluation of family history of the condition
• Laboratory testing for blood oxygenation, autoantibodies, blood in urine, and others
• Imaging of lungs, joints, and kidneys: Chest X-rays often show diffuse whiteness reflecting interstitial lung disease pattern
• Pulmonary function testing
• Genetic testing for a mutated COPA gene

COPA Syndrome is best thought of as an autoinflammatory disease (AID), but because the mutation also causes immune dysregulation, many of the classic autoimmune disease marker tests will be positive This includes rheumatoid factor (RF), antinuclear antibodies (ANA) and the anti-neutrophil cytoplasmic antibody (ANCA) family of tests.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of COPA Syndrome?

Complications of COPA Syndrome may include 

• End-stage pulmonary disease requiring lung transplantation
• End-stage kidney disease requiring kidney transplantation
• Severe arthritis with a decrease in strength and mobility 
• Overall, reduced quality of life

How is COPA Syndrome Treated?

Treatment for COPA Syndrome is directed toward decreasing the abnormal inflammatory response and may include:

• Systemic corticosteroids
• Immunosuppressives including cyclophosphamide, methotrexate, azathioprine, hydroxychloroquine, etanercept, mycophenolate mofetil, intravenous Immunoglobulins (IVIG), rituximab, and baricitinib
• The healthcare professional may prescribe other medications to manage any additional symptoms or signs

Individuals with end-stage lung or renal disease may be considered for organ transplantation.

How can COPA Syndrome be Prevented?

Presently, it is not possible to prevent COPA Syndrome as the cause is due to genetic factors.

• Genetic counseling and testing may be recommended for individuals with a family history of the disorder and couples planning to have children
• However, early diagnosis and appropriate treatment can help manage the symptoms and prevent complications

What is the Prognosis of COPA Syndrome? (Outcomes/Resolutions)

The prognosis for COPA Syndrome varies depending on the severity of the disorder and the effectiveness of the treatment. 

• With suitable treatment, most patients with COPA Syndrome can have an improved quality of life
• However, the disorder can cause significant functional limitations and end-stage organ disease if left untreated

Additional and Relevant Useful Information for COPA Syndrome:

The following link is a useful resource for information on other rare conditions on DoveMed:

https://www.dovemed.com/diseases-conditions/rare-disorders/