Glutaric Acidemia Type II Disorder

Other Names

Glutaric Acidemia II (GA2, GA II)
Glutaric Aciduria Type 2
Multiple Acyl-CoA Dehydrogenase Deficiency (MAD, MADD)
Electron Transfer Flavoprotein Dehydrogenase Deficiency (ETFA, ETFB, ETFDH)

Diagnosis Coding

E71.313, Glutaric Aciduria type II

Disorder Category

A fatty acid oxidation disorder

Frequency

Glutaric Acidemia type II is a very rare disorder; its precise incidence is unknown. It has been reported in several different ethnic groups. Prevalence is about 1:250,000 live births. [Schulze: 2003] Sudden infant death syndrome (SIDS) in siblings is possible.

Prognosis

Children and adults who receive treatment for glutaric acidemia, type II (GA-2) can lead healthy lives. Some children who receive treatment may still experience some learning disabilities. Without treatment, children and adults with GA-2 are at risk of liver damage, heart trouble, or brain damage.

Signs and Symptoms

Signs of Glutaric Acidemia, Type II (GA-2) can begin shortly after birth, in childhood, or even adulthood. Signs of GA-2 include:

Sleeping longer or more often
Behavior changes
Irritability
Weak muscle tone (known as Hypotonia)
Poor appetite
Fever
Vomiting
Diarrhea
Low blood sugar (called hypoglycemia)
Trouble breathing
A “sweaty feet” smell
Seizures (epilepsy)
Birth defects

Many of these signs may occur when your baby eats foods that their body cannot break down. They can be triggered by long periods of time without eating, illnesses, and infections.

Children who have this disorder have low blood sugar when their stomach is empty (called fasting hypoglycemia), a severe buildup of acid in the blood (metabolic acidosis), and an increase in ammonia in the blood (hyperammonemia).

Glutaric Acidemia type II usually appears in infancy or early childhood as a sudden episode called a metabolic crisis, in which acidosis and low blood sugar (hypoglycemia) cause weakness, behavior changes such as poor feeding and decreased activity, and vomiting. These metabolic crises, which can be life-threatening, may be triggered by common childhood illnesses or other stresses.

In the most severe cases of Glutaric Acidemia Type II, affected individuals may also be born with physical abnormalities. These may include brain malformations, an enlarged liver (hepatomegaly), a weakened and enlarged heart (dilated cardiomyopathy), fluid-filled cysts and other malformations of the kidneys, unusual facial features, and genital abnormalities. Glutaric acidemia type II may also cause a characteristic odor resembling that of sweaty feet.

Some affected individuals have less severe symptoms that begin later in childhood or in adulthood. In the mildest forms of glutaric acidemia type II, muscle weakness developing in adulthood may be the first sign of the disorder.

Cause

Glutaric Acidemia type II is an inherited disorder that interferes with the body’s ability to break down proteins and fats to produce energy. Incompletely processed proteins and fats can build up in the body and cause the blood and tissues to become too acidic (metabolic acidosis).

Diagnosis

Doctors diagnose glutaric acidemia type II by analyzing the blood to look for a buildup of certain molecules. Tests of skin cells are done to look for levels of certain enzymes. Genetic testing is also available.

Screening Finding

Elevated C4 and C5

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=100%

Follow up testing

Quantitative plasma acylcarnitine profile, urine organic acid and acylglycine analysis, confirmation with ETF/ETF-QO enzyme assay and/or gene sequencing. If negative, consider riboflavin transporter deficiency if biochemical abnormalities (plasma acylcarnitine profile) are persistent.

Care Management

Upon Notification of the + Screen
- Contact the family and evaluate the infant for facial dysmorphism, poor feeding, vomiting, lethargy, odor of sweaty feet.
- Provide emergency treatment/referral for signs or symptoms of hypoketotic hypoglycemia, metabolic acidosis, hyperammonemia, cardiomyopathy (see ACT Sheet for Glutaric Acidemia Type 2 (C4 & C5) (ACMG) (PDF Document 347 KB)
- To confirm the diagnosis, work with the following service(s): Newborn Screening Services

For evaluation and ongoing collaborative management, consult the following service(s): Pediatric Genetics

If the Diagnosis is Confirmed

Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill.
Support implementation and maintenance of low fat, low protein diet.
Oral L-Carnitine, Riboflavin, or Glycine supplements may be indicated.

For those identified after irreversible consequences, assist in the management, particularly with developmental and educational interventions.

Treatment

Treatment of glutaric acidemia type II is similar to that for MCAD deficiency, except that doctors may give supplements of riboflavin (vitamin B2).
Patients may be advised to follow a diet low in fat and protein and high in carbohydrates, particularly in severe cases. Depending on the subtype, riboflavin (100-400 mg/day), coenzyme Q10 (CoQ10), L-carnitine, or glycine supplements may be used to help restore energy production.
Some small, uncontrolled studies have reported that racemic salts of beta-hydroxybutyrate were helpful in patients with moderately severe disease; further research is needed.

References

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