Metabolic Conditions

Glutaric Acidemia Type II

Robert Tomaino, Medical Writer
5/24/2004

Synopsis:
Glutaric acidemias (GA) are rare inborn errors of metabolism marked by the abnormal accumulation of glutaric acids and other chemicals in the blood and tissues of the body. There are two forms of glutaric acidemia: GA type I and GA type II. Glutaric acidemias are classified as organic acidemias. GA type II is further classified as a fatty acid oxidation disorder.

Synonyms:
GA type II:
Glutaric aciduria type II
Multiple acyl-CoA dehydrogenation deficiency
MADD

Causes:
Glutaric acidemia type II is a genetic disorder that results from a mutation of one of three different genes located on chromosomes 19, 15, and 4. Mutations of these genes result in deficiency of certain enzymes (i.e., electron transfer flavoprotein (ETF), ETF-ubiquinone oxidoreductase (ETF-QO), or ETF dehydrogenase). These enzymes are needed to metabolize (breakdown) certain chemicals in the body.

The genetic mutations associated with glutaric acidemias are inherited in an autosomal recessive manner. The symptoms of glutaric acidemias result from the accumulation of glutaric acids and other chemicals in the blood and tissues of the body. Accumulation of these chemicals has toxic effects on various organ systems of the body.

Symptoms:
The specific symptoms of glutaric acidemia type II may vary greatly. The disorder usually follows one of three expressions: a severe form that affects newborns; a severe form that affects newborns and is associated with congenital anomalies; and a milder form that occurs later during childhood or adulthood. In newborns, symptoms may include:

• Metabolic acidosis - elevated levels of acids in the blood and tissues
• Hypoglycemia
• Distinct odor similar to "sweaty feet"
• Hypotonia
• Hepatomegaly

Some newborns with GA type II may also have congenital anomalies, including:

• Enlarged, malformed kidneys with multiple cysts
• Distinct facial features -e.g., malformed ears, high forehead, eye abnormalities
• Genital abnormalities

In both newborn forms of GA type II, life-threatening complications may develop during infancy including cardiomyopathy (heart muscle disease), significantly elevated levels of acids in the blood and tissues (severe metabolic crisis), and coma.

The late-onset, milder form of GA type II varies greatly. Symptoms may include vomiting, lethargy, muscle weakness, hypoglycemia, cardiomyopathy, and coma.

Diagnosis:
Many infants with glutaric acidemia may be diagnosed through newborn screening (however, this is not offered in all 50 states, Supplemental Newborn Screening should be done), a process in which blood is taken from the heels of an infant. Several tests are performed on the blood samples that may detect glutaric acidemia. For example, enzyme assay may detect decreased activity certain enzymes in certain white blood cells (leukocytes) and connective tissue cells (fibroblasts). Analysis of urine samples may reveal elevated levels of glutaric and other acids that may be indicative of glutaric acidemia.

Prenatal diagnosis of glutaric acidemia is possible through amniocentesis. Amniocentesis is a common prenatal procedure in which a small amount of amniotic fluid (the protective fluid that surrounds a fetus) is removed and studied. Excess glutaric acid in amniotic fluid is indicative of glutaric acidemia.

A diagnosis of GA type II may be made by an acylcarnitine profile test. During this test, blood or tissue samples are taken and studied to detect and analyze acylcarnitine, a substance that builds up in individuals with fatty acid oxidation disorders (FODs) like GA type II. Each FOD has a unique acylcarnitine profile allowing physicians to confirm a diagnosis of a FOD and to determine which specific FOD is present.

Treatment:
Various treatment options in children with the severe, neonatal form of GA type II have been ineffective. Mild or late-onset forms of GA type II have responded to a strict, Fat and protein-deficient diet supplemented with L-carnitine and riboflavin.

Summary:
Glutaric acidemias are rare, metabolic disorders that are under-diagnosed. GA type I is often misdiagnosed as cerebral palsy. Prompt diagnosis and treatment is essential for infants with these disorders. However, significant symptoms may still occur despite treatment and proper diet, especially in severe forms. Mild forms of glutaric acidemia respond to a protein restricted diet and supplemental treatment.

Review Date: 7/26/2004 Reviewed By: Douglas R. Stewart, M.D., Division of Medical Genetics, Hospital of the University of Pennsylvania, Philadelphia, PA. Review provided by VeriMed Healthcare Network.
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