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

• Aldosterone Synthase Deficiency Disorder
• Steroid 18-Hydroxylase Deficiency Disorder
• Steroid 18-Oxidase Deficiency Disorder

What is Corticosterone Methyloxidase Deficiency Disorder? (Definition/Background Information)

• Corticosterone Methyloxidase Deficiency Disorder is a rare genetic disorder. This disorder is reportedly more common in Iranian Jewish populations and the Amish population of Philadelphia, USA
• Corticosterone Methyloxidase Deficiency Disorder is generally caused by mutations in the CYP11B2 gene. This gene codes for the enzyme aldosterone synthase, which regulates the synthesis of the hormone aldosterone
• Aldosterone regulates salt and water balance within the human body. Therefore, when aldosterone synthesis is impaired, salt and ionic imbalances ensue, leading to metabolic acidosis, hyponatremia, and hyperkalemia. Hence, the condition is also known as Aldosterone Synthase Deficiency Disorder
• The signs and symptoms of Corticosterone Methyloxidase Deficiency Disorder include salt loss in urine, reduced potassium in urine, dehydration, and muscle weakness. In infants with this deficiency disorder, seizures, coma, and death are known to occur. The symptoms are reported to become milder with age
• A diagnosis of Corticosterone Methyloxidase Deficiency Disorder may require a physical examination, an assessment of family history, blood tests to check for hormone levels, and DNA testing to look for CYP11B2 gene mutations
• Treatment options for Corticosterone Methyloxidase Deficiency Disorder can include rehydration, mineralocorticoids supplementation, and inclusion of sodium in the diet
• Corticosterone Methyloxidase Deficiency Disorder is a genetic condition and there are currently no preventive methods or guidelines available. Prospective parents with a history of Corticosterone Methyloxidase Deficiency Disorder may benefit from genetic testing and counseling in order to better understand the risks of having a child
• The prognosis of Corticosterone Methyloxidase Deficiency Disorder depends upon the severity of the signs and symptoms; individuals with mild signs and symptoms have better life expectancies than those with severe signs and symptoms

Who gets Corticosterone Methyloxidase Deficiency Disorder? (Age and Sex Distribution)

• Corticosterone Methyloxidase Deficiency Disorder is reported to be a rare condition with an unknown prevalence
• This congenital deficiency disorder generally affects newborns within the first 5 months of life. In a majority though, the signs and symptoms manifest within 5 days of birth
• The condition can potentially affect both male and female genders
• Even though all races and ethnic groups are at risk, the disorder is reported to be more common among the following groups:
  • The Amish population in Lancaster, Philadelphia, USA
  • The Persian (Iranian) Jewish population

What are the Risk Factors for Corticosterone Methyloxidase Deficiency Disorder? (Predisposing Factors)

• A major risk factor for Corticosterone Methyloxidase Deficiency Disorder is a family history of the disorder
• Individuals of Amish descent in the US and Jewish ancestry in Iran have a higher risk for this type of 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 ones 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 Corticosterone Methyloxidase Deficiency Disorder? (Etiology)

Corticosterone Methyloxidase Deficiency Disorder is caused by mutations in the CYP11B2 gene. It is inherited in an autosomal recessive manner.

• The CYP11B2 gene codes for an enzyme known as aldosterone synthase, which regulates the synthesis of the hormone aldosterone, via a 3-step process: 11-deoxycorticosterone to corticosterone, corticosterone to 18-hydroxycorticosterone, and 18-hydroxycorticosterone to aldosterone
• The seat of synthesis of aldosterone synthase is the adrenal glands. Aldosterone in turn, regulates blood pressure by regulating salt and water levels within the body
• A mutation in the CYP11B2 gene leads to insufficient amount of aldosterone, which was previously known as corticosterone methyloxidase. The insufficient amount of this enzyme leads to a loss of salt (sodium chloride) through urine, as well as reduced release of potassium in urine
• The resultant salt/ion imbalance is the primary reason for the observed symptoms of Corticosterone Methyloxidase Deficiency Disorder

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 Corticosterone Methyloxidase Deficiency Disorder?

The main symptoms of Corticosterone Methyloxidase Deficiency Disorder are due to metabolic acidosis (high acid content in blood), hyponatremia (low levels of sodium in blood), and hyperkalemia (high potassium levels in blood) that occur as a consequence of insufficient amounts of the enzyme aldosterone.

In infants, the above conditions may cause symptoms such as:

• Dehydration
• Salt wasting
• Nausea and vomiting
• Low blood pressure
• Seizures

The typical symptoms through childhood include the following:

• Dehydration
• Low blood pressure
• Failure to reach developmental milestones
• Short stature
• Weakness
• Dizziness
• A craving for salt

How is Corticosterone Methyloxidase Deficiency Disorder Diagnosed?

A diagnosis of Corticosterone Methyloxidase Deficiency Disorder may involve the following:

• Physical examination
• Family medical history evaluation
• Assessment of symptoms
• Blood tests to check for:
  • Elevated plasma-renin activity : serum aldosterone ratio
  • Elevated serum 18-hydroxycorticosterone : aldosterone ratio
  • Serum 18-OHB to aldosterone ratio
  • Levels of hormones 
• Genetic testing to check for CYP11B2 gene mutations

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 Corticosterone Methyloxidase Deficiency Disorder?

Some of the potential complications of Corticosterone Methyloxidase Deficiency Disorder include:

• Failure to gain weight (failure to thrive in infants)
• Seizures and coma in infants, may be life-threatening
• Short stature in children

How is Corticosterone Methyloxidase Deficiency Disorder Treated?

The treatment may be instituted in many cases based upon the signs and symptoms, even before the disorder is confirmed through genetic test. The treatment options for Corticosterone Methyloxidase Deficiency Disorder may include:

• Maintaining fluid levels in order to combat dehydration
• Hydrocortisone and fludrocortisone administration in infants to overcome salt-wasting
• Replacement of aldosterone with mineralocorticoids such as 9 alpha-fluorohydroxycortisone; mineralocorticoids are a class of corticosteroid hormones
• In children, increased sodium in diet to overcome a tendency for sodium deprivation under conditions such as diarrhea

How can Corticosterone Methyloxidase Deficiency Disorder be Prevented?

• Currently, there are no specific methods or guidelines to prevent Corticosterone Methyloxidase Deficiency Disorder, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) 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 prior to planning for a child
• Active research is currently being performed in order to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Corticosterone Methyloxidase Deficiency Disorder
• Regular medical screening at periodic intervals with tests, and physical examinations are strongly recommended

What is the Prognosis of Corticosterone Methyloxidase Deficiency Disorder? (Outcome/Resolutions)

• The prognosis of Corticosterone Methyloxidase Deficiency Disorder is based on the severity of the signs and symptoms
• In general, infants with mild signs and symptoms have better prognosis than those with severe signs and symptoms. The symptoms are reported to become milder as the child ages and reaches adulthood
• If the newborn baby survives the initial phase (neonatal symptoms), then the prognosis is generally improved. In such cases, the life expectancy is expected to be normal with regular care and appropriate treatment, as the child develops

Additional and relevant useful information for Corticosterone Methyloxidase Deficiency Disorder:

• Congenital adrenal hyperplasia (CAH) is a group of genetic disorders that leads to low production of vital adrenal cortex hormones. Cortisol and aldosterone are not adequately produced in individuals with CAH, which upsets the balance of hormones in the body

The following link will help you understand congenital adrenal hyperplasia:

http://www.dovemed.com/diseases-conditions/congenital-adrenal-hyperplasia/