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

• CBG Deficiency Disorder
• Transcortin Deficiency Disorder

What is Corticosteroid-Binding Globulin Deficiency Disorder? (Definition/Background Information)

• Corticosteroid-Binding Globulin (CBG) Deficiency Disorder is a genetic disorder characterized by extreme tiredness (fatigue), particularly after physical exertion, and low blood pressure (hypotension)
• Corticosteroid-binding globulin (CBG) is a protein primarily produced in the liver that attaches to cortisol, a hormone with numerous functions, including maintaining blood sugar levels, protecting the body from stress, and suppressing inflammation. When cortisol is needed in the body, CBG delivers the cortisol where it is needed and releases it
• Signs and symptoms of CBG Deficiency Disorder vary. While some individuals may experience no symptoms, others are found to have a fatty liver and chronic pain. Some people with CBG Deficiency Disorder also have chronic fatigue syndrome
• Corticosteroid-Binding Globulin Deficiency Disorder is caused by mutations in the SERPINA6 gene. The SERPINA6 gene is commonly also referred to as the CBG gene. Both autosomal dominant and autosomal recessive inheritance have been reported
• While there is still no cure, the treatment options for Corticosteroid-Binding Globulin Deficiency Disorder will depend on the type and severity of symptoms present and may involve several specialists

(Source: Corticosteroid-Binding Globulin Deficiency; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets Corticosteroid-Binding Globulin Deficiency Disorder? (Age and Sex Distribution)

• Corticosteroid-Binding Globulin Deficiency Disorder is a rare congenital disorder. The age at which presentation of symptoms occurs is variable
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Corticosteroid-Binding Globulin Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Corticosteroid-Binding Globulin Deficiency Disorder can be inherited
• Currently, no other risk factors have been clearly identified for CBG Deficiency 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 Corticosteroid-Binding Globulin Deficiency Disorder? (Etiology)

• Corticosteroid-Binding Globulin Deficiency Disorder is caused by mutations in the SERPINA6 gene. The SERPINA6 gene is commonly also referred to as the CBG gene
• Corticosteroid-binding globulin (CBG) is a protein primarily produced in the liver that attaches to cortisol, a hormone with numerous functions, including maintaining blood sugar levels, protecting the body from stress, and suppressing inflammation. When cortisol is needed in the body, CBG delivers the cortisol where it is needed and releases it
• Both autosomal dominant and autosomal recessive inheritance have been reported

(Source: Corticosteroid-Binding Globulin Deficiency; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Autosomal dominant: 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 function 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.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Corticosteroid-Binding Globulin Deficiency Disorder?

The signs and symptoms of Corticosteroid-Binding Globulin Deficiency Disorder may vary among affected individuals in type and severity, and may include:

• Abnormality of metabolism/homeostasis
• Hypotension
• Increased muscle fatiguability

(Source: Corticosteroid-Binding Globulin Deficiency; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

• Headaches
• Sore throat

How is Corticosteroid-Binding Globulin Deficiency Disorder Diagnosed?

Corticosteroid-Binding Globulin Deficiency Disorder is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm SERPINA6 gene mutation(s)

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 Corticosteroid-Binding Globulin Deficiency Disorder?

The complications of Corticosteroid-Binding Globulin Deficiency Disorder may include:

• Chronic fatigue syndrome
• Reduced quality of life due to fatigue interfering with day-to-day activities

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Corticosteroid-Binding Globulin Deficiency Disorder Treated?

There is no cure for Corticosteroid-Binding Globulin Deficiency Disorder, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Corticosteroid-Binding Globulin Deficiency Disorder be Prevented?

Corticosteroid-Binding Globulin Deficiency Disorder may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Corticosteroid-Binding Globulin Deficiency Disorder ? (Outcomes/Resolutions)

• The prognosis of Corticosteroid-Binding Globulin Deficiency Disorder is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Corticosteroid-Binding Globulin Deficiency Disorder:

The following DoveMed website link is a useful resource for additional information:

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