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

• Electron Transfer Flavoprotein Dehydrogenase Deficiency
• ETFB Deficiency
• GA II (Glutaric Acidemia Type II)

What is Glutaric Acidemia Type II? (Definition/Background Information)

• Glutaric Acidemia Type II (or GA II) is a rare inherited genetic disorder. In this disorder, a defective breakdown of proteins and fats, result in the accumulation of acidic products in the body
• Accumulation of acidic products in the tissues, results in a clinical condition, called metabolic acidosis. This may lead to mild or severe signs and symptoms, which can include developmental malformations
• Often, symptomatic treatment is provided right from birth, which could include oral medications and intravenous injections
• The prognosis depends on the severity of the disorder and is usually poor, if the symptoms are severe

Who gets Glutaric Acidemia Type II? (Age and Sex Distribution)

• Glutaric Acidemia Type II is a rare disorder that is present at birth, but it may not manifest until adulthood, in some cases
• Both males and females are affected
• Very few cases of GA II have been reported worldwide and it is observed that this disorder is not confined to any race, ethnic group, or certain geographical regions of the world

What are the Risk Factors for Glutaric Acidemia Type II? (Predisposing Factors)

Glutaric Acidemia Type II is an autosomal recessive genetic disorder; those, with a family history of the condition have a high risk of inheriting the same.

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 Glutaric Acidemia Type II? (Etiology)

• Glutaric Acidemia Type II is caused by mutations in any one of the following 3 genes: ETFA, ETFB, or ETFDH gene. These genes are responsible for making proteins, called electron transfer, necessary for the body's energy producing process
• The defective proteins, due to genetic mutations are called electron transfer flavoprotein and electron transfer flavoprotein dehydrogenase. These enzymes are found in a part of the cell, called the mitochondria
• The defective proteins in GA II cause abnormal metabolism of proteins and fats, obtained from the diet. Such defective processes, results in the accumulation of substances that are not fully metabolized. This abnormal and unwanted accumulation of partially digested food products, lead to cell damage
• Defective proteins may either result in a complete loss, or a partial loss of protein activity. A complete loss of activity, leads to severe signs and symptoms. When such a loss of activity is partial, it results in milder signs and symptoms
• GA II is a genetic disorder that is inherited in an autosomal recessive pattern

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 Glutaric Acidemia Type II?

The signs and symptoms of Glutaric Acidemia Type II appears early in life. In some cases, these are severe and occur within a few days of birth. In others, the signs and symptoms occur, during the first few years of life. In mildest forms, the signs and symptoms do not appear until adulthood.

• The most common symptom in mild cases is muscle weakness
• The signs and symptoms may develop either gradually, or they may be sudden, which is called a metabolic crisis
• Metabolic crisis is usually triggered by infection or some other type of body stress, resulting in potentially life-threatening situations, wherein prompt medical attention becomes necessary. Metabolic crisis signs and symptoms include:
  • Low blood sugar (hypoglycemia) resulting in generalized body weakness
  • Excessive crying
  • Vomiting
  • Bad body odor
  • Poor feeding
  • Decreased body movement activity
• Severe cases of Glutaric Acidemia Type II, not only have severe clinical presentations, but also increased frequency of physical deficiencies, such as:
  • Abnormally large heart (cardiomegaly)
  • Large kidney with multiple cysts
  • Facial abnormalities
  • Enlarged liver (hepatomegaly)
  • Abnormal sexual organs

How is Glutaric Acidemia Type II Diagnosed?

A diagnosis of Glutaric Acidemia Type II would involve:

• Physical exam with evaluation of medical history
• The screening of newborns having a family history the disorder is very important
• Urine and blood analysis
• Genetic analysis to detect mutations
• Skin biopsy

What are the possible Complications of Glutaric Acidemia Type II?

Complications of Glutaric Acidemia Type II include:

• Severe congenital abnormalities that affect the liver, heart, kidney, brain, and genitalia
• Muscular and skeletal defects
• Low blood sugar, which can cause brain damage, if not treated promptly in individuals with metabolic crisis

How is Glutaric Acidemia Type II Treated?

Glutaric Acidemia Type II usually manifests immediately on birth. This would require rapid and intense methods to effectively control its harmful effects. Individuals, in whom a late onset of the condition is seen, the treatment may include diet control and medication.

• In mild cases, oral medication is often administered to help the body process reduced levels of glutaric acid, or to eliminate wastes from the body quicker. Oral medications may include vitamin B2 (riboflavin) and carnitine supplements
• If the condition is serious (termed as a metabolic crisis), intravenous injections, like carnitine, glucose, and insulin, are provided
• Frequent feeding is advised (every 4-6 hours for an infant) so as to prevent any metabolic adversities; special medical formulas for babies are also available
• A prescribed diet containing low levels of protein and fat, but higher amounts of carbohydrates, have to be followed; fasting has to be avoided at all times
• Regular blood and urine tests are required, if any signs of fever, vomiting, illness, sleeplessness, or appetite loss are noticed in the child. In such cases, prompt medical attention has to be provided
• Occupational and physical therapy may be provided for muscular ailments and abnormalities

How can Glutaric Acidemia Type II be Prevented?

• Currently, there are no specific methods or guidelines to prevent Glutaric Acidemia Type II 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, 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

What is the Prognosis of Glutaric Acidemia Type II? (Outcomes/Resolutions)

• Children with Glutaric Acidemia Type II require prompt, continuous, and lifelong medical support and management of the condition. A strict diet compliance has to be maintained always, in order to limit progression of the disorder
• Infants and newborns with congenital defects and those suffering from acute forms of the disorder, have the worst outcomes. In such cases, the prognosis of GA II is very poor and the survival rate is extremely low
• The recurrence of metabolic crises may reduce with an advancing age. However, in spite of treatment, in some children, long-term muscular damage and neurological complications may occur

Additional and Relevant Useful Information for Glutaric Acidemia Type II:

• GA II is a potentially fatal disorder. All children suffering from the condition must carry with them an emergency protocol sheet, explaining the steps that need be taken, in case of a crisis. This must be informed to all concerned, like the teachers, caretakers, relatives, babysitters, etc.
• There are voluntary organizations and support groups that provide help and understanding to the families and parents of the Glutaric Acidemia Type II disorder affected