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

• Deficiency of Medium Chain Acyl-CoA Dehydrogenase
• MCADH Deficiency Disorder
• Medium Chain Acyl CoA Dehydrogenase Deficiency Disorder

What is Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder? (Definition/Background Information)

• Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency (MCADD) Disorder is an inherited metabolic disorder that prevents the body from converting certain fats to energy, particularly during periods without food (fasting)
• People with MCADD Disorder do not have enough of an enzyme needed to metabolize a group of fats called medium-chain fatty acids
• The signs and symptoms usually begin by early childhood and may include vomiting, lack of energy, and low blood sugar (hypoglycemia). Symptoms can be triggered by periods of fasting or by illnesses
• MCADD is caused by mutations in the ACADM gene and inheritance is autosomal recessive
• Treatment includes strict avoidance of fasting and avoidance of medium chain triglycerides in the diet
• If not treated, people with Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder are at risk of serious complications including sudden death

(Source: Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder? (Age and Sex Distribution)

• Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency is a rare congenital disorder
• The presentation of symptoms are seen in infants and young children
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder can be inherited
• Currently, no risk factors have been clearly identified for 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 Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder? (Etiology)

Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder is caused by mutations in the ACADM gene. This gene gives the body instructions for making an enzyme called medium-chain acyl-CoA dehydrogenase, needed to break down fats called medium-chain fatty acids.

• These fatty acids are found in foods and the body's tissues, and are an important source of energy for the heart, muscles, liver, and other tissues. Mutations in this gene lead to low levels of the enzyme, which means that medium-chain fatty acids are not broken down properly. They cannot be converted to energy, leading to the symptoms of MCADD Disorder
• Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency (MCADD) Disorder is inherited in an autosomal recessive manner
• This means that to have MCADD Disorder, a person must have a mutation in both copies of the responsible gene in each cell. There is nothing either parent can do, before or during a pregnancy, to cause a child to have this condition.
• People with MCADD inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected)

(Source: Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

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 Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder?

The signs and symptoms of Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder may include:

• Cerebral edema
• Coma
• Decreased plasma carnitine
• Elevated hepatic transaminases
• Generalized hypotonia
• Hepatic steatosis
• Hepatomegaly
• Hyperglycinuria
• Hypoglycemia
• Lethargy
• Medium chain dicarboxylic aciduria
• Seizures
• Vomiting

(Source: Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder Diagnosed?

A diagnosis of Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder requires an evaluation of a person's symptoms as well as the interpretation of several tests.

Initial testing may include:

• Plasma acylcarnitine
• Urine organic acid
• Urine acylglycine              

Further testing to confirm the diagnosis may include molecular genetic testing of the ACADM gene or biochemical genetic testing. MCADD is included in many newborn screening programs, so a newborn with MCADD who does not yet exhibit symptoms may be diagnosed early. If a newborn screening result for MCADD is not in the normal range ("positive"), additional testing can then be ordered.

(Source: Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

What are the possible Complications of Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder?

The complications of Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder may include:

• Liver damage and loss of liver function
• Coma, which may even result in death

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

How is Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder Treated?

• Treatment includes strict avoidance of fasting and avoidance of medium chain triglycerides in the diet
• If not treated, people with Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder are at risk of serious complications including sudden death

(Source: Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder be Prevented?

Currently, Medium-Chain Acyl-Coenzyme A Dehydrogenase 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) 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 Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder? (Outcomes/Resolutions)

• The prognosis of Medium-Chain Acyl-Coenzyme A Dehydrogenase 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 Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder:

Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Disorder is also known by the following names:

• ACADM Deficiency Disorder
• MCAD Deficiency Disorder
• MCADD Disorder

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

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