General Condition Information
Other Names
- 3 methylglutaconyl CoA hydratase deficiency
- 3-methyglutaconic aciduria
- 3-methyl-glutaconyl coA hydratase deficiency
- 3-methylglutaconic acidemia
- 3-methylglutaconic acidemia, type 1
- 3-methylglutaconyl CoA hydratase deficiency
- 3-methylglutaconyl-CoA hydratase deficiency
- 3-Methylglutaconyl-CoA Hydratase Deficiency Aciduria
- 3-methylglutaconyl-CoA hydratase deficiency, Barth syndrome, Costeff syndrome
Condition Type
Birth Prevalence
It is unknown how many babies are born with this rare condition each year in the United States.
Screening Finding
What is 3-methylglutaconic aciduria
3-Methylglutaconic aciduria is caused by a group of inherited (genetic) conditions that prevent the body from making energy properly. There are five different types of 3-methylglutaconic aciduria that change the way the body makes energy. Each condition causes a buildup of an acid called 3-methylglutaconic acid in your baby’s body. When acid builds up in your urine, it is called aciduria.
Type I is also called 3-methylglutaconyl-CoA hydratase deficiency, named for the enzyme you need to process a part of proteins called leucine. When your baby cannot make enough working enzyme, toxins build up and can damage their brain and nerves.
Type II is also called Barth syndrome, named after the doctor who first described it. In Barth syndrome, the body is unable to make a protein called tafazzin properly. Tafazzin plays an important role in building your mitochondria, the parts of your cells that produce energy. When mitochondria do not work properly, the body has trouble making energy. Without enough energy, their heart and muscles get weak.
Type III is also called Costeff syndrome, also named after the doctor who first described it. In Costeff syndrome, the body is unable to make a protein called OPA3 properly. OPA3 is also found in the mitochondria. Not having enough working enzyme damages the eyes and brain.
Type IV does not have a defined cause. If your baby has 3-methylglutaconic aciduria and does not have Type I, II, III, or V, they will be considered Type IV.
Type V is also called dilated cardiomyopathy with ataxia (DCMA) syndrome. In DCMA syndrome, the body is unable to make a protein called DNAJC19 properly. DNAJC19 is found in the mitochondria as well. Not having enough working enzyme damages your heart and brain.
A lack of energy and increased toxins leads to the wide range of signs and symptoms of these conditions.
Newborn Screening and Follow-Up
Newborn screening for 3-methylglutaconic aciduria is done using a small amount of blood collected from your baby’s heel. To learn more about this process, visit the Blood Spot Screening page.
During screening, a special machine measures how much of certain substances (called acylcarnitines) are in your baby’s blood. Your body makes these substances when it breaks down food. Babies with high levels of these substances might have 3-methylglutaconic aciduria. Newborn screening cannot tell what type of 3-methylglutaconic aciduria a baby might have. Follow-up testing will help determine if your baby has 3-methylglutaconic aciduria and which type your baby has.
If your baby’s blood spot screening result for 3-methylglutaconic aciduria is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.
An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing. An out-of-range result can mean that your baby has one of several possible conditions. It is important to do follow-up testing to correctly identify the condition causing your baby’s result.
To learn more about screening results, visit the Blood Spot Screening Results page.
Your baby may need the following tests after an out-of-range screening result:
- Blood and/or urine tests
- Genetic testing using a blood sample
You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems soon after birth if they are not diagnosed and treated quickly.
False-positive newborn screening results for this condition are rare. Babies who are born early (premature) may have out-of-range results.
Some babies may have a false-positive result for 3-methylglutaconic aciduria because their mother has high acylcarnitine levels. These babies do not have and will not develop 3-methylglutaconic aciduria. More testing on both mom and baby will determine who has high acylcarnitine levels.
Condition Details
Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.
Signs of 3-methylglutaconic aciduria vary by type. For all types, signs begin before birth or at birth.
Signs of the condition may include the following:
Type I:
- Developmental delays
- Irregular, uncontrolled muscle movements
- Muscle spasms and weakness in the arms and legs
- Coma
- Growing slowly or gaining weight slowly (failure to thrive)
Type II:
- Frequent infections
- Weak muscles
- Delayed growth
- Heart problems
Type III:
- Vision loss
- Trouble with balance
- Floppy arms and legs (hypotonia)
- Irregular, uncontrolled muscle movements
Type IV:
- Symptoms vary by individual
- May have signs similar to types I, II, or III
Type V:
- Difficulty moving muscles (ataxia)
- Delayed growth
- Heart Problems
The condition is caused by a change in the AUH (Type I), TAZ (Type II), OPA3 (Type III), or DNAJC19 (Type V) genes. These genes give your body instructions to make and maintain mitochondria, the part of your cells that makes energy.
Without these working genes, the mitochondria in your baby’s body cannot support proper food breakdown, energy creation, or waste removal.
3-Methylglutaconic aciduria is caused by a genetic condition. Babies inherit genetic conditions from their biological (birth) parents. To learn more about genetic conditions, visit MedlinePlus Genetics.
- 3-Methylglutaconic aciduria Types I, III, and V are autosomal recessive conditions. Babies inherit the condition when each parent passes down the same nonworking gene that causes 3-methylglutaconic aciduria (AUH, OPA3, or DNAJC19) to their baby. Only babies with two matching nonworking genes—for example, one nonworking AUH from the mom and one nonworking AUH from the dad—have this condition. Babies with two nonworking genes that do not match—for example, one nonworking AUH from the mom and one nonworking OPA3 from the dad—will not have this condition.
- People with one working copy and one nonworking copy of the AUH, OPA3, or DNAJC19 gene are called carriers.
- Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children.
- If two parents are carriers of a nonworking copy of the AUH, OPA3, or DNAJC19 gene, they have a 1 in 4 chance of having a child with 3-methylglutaconic aciduria.
- Carriers for 3-methylglutaconic aciduria often do not know they are carriers before having a child with the condition. In most cases, families have no history of the condition until the birth of a child with 3-methylglutaconic aciduria.
- Parents who already have a child with 3-methylglutaconic aciduria due to a change in the AUH, OPA3, or DNAJC19 gene still have a 1 in 4 chance of having another child with 3-methylglutaconic aciduria. This 1 in 4 chance stays the same for all future children.
- 3-Methylglutaconic aciduria type II is inherited in an X-linked recessive pattern. Babies inherit the condition on the X chromosome, which is one of the two sex chromosomes.
- When boys (who only have one X chromosome) receive one nonworking copy of the TAZ gene from their mom, they have this condition. Dads cannot pass on the condition to their sons.
- Girls (who have two X chromosomes) must receive two nonworking TAZ genes—one from the mom and one from the dad—to have this condition.
- Because these conditions are linked to the X chromosome, they are much more common in boys than girls.
- Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it. Visit the National Society of Genetic Counselors to find a genetic counselor and the American College of Medical Genetics and Genomics to find a medical geneticist.
Treatment and Management
It is important to talk to your health care provider about which treatment(s) are best for your baby. Treatment will depend on the type of 3-methylglutaconic aciduria your baby has. The goal of treatment is to prevent the health problems caused by these conditions.
Treatments may include the following:
- Regular visits with a heart doctor (cardiologist)
- Regular visits with an eye doctor (ophthalmologist)
- L-carnitine supplementation
- Antibiotics
Children who receive early and ongoing treatment specific for their type of 3-methylglutaconic aciduria can live longer than untreated children.