Conditions 2-Methyl-3-Hydroxybutyric Acidemia

2-methyl-3-hydroxybutyric acidemia (2M3HBA) is an inherited condition in which the body is unable to break down certain proteins. This condition may also affect the body’s ability to break down certain fatty acids and to regulate some activities of the nervous system. 2M3HBA is considered an organic acid condition because it can lead to a harmful amount of certain organic acids and toxins in the body. Early diagnosis and treatment have been shown to be effective in improving the health of individuals affected by 2M3HBA.

Condition Type

Organic Acid Conditions


2-methyl-3-hydroxybutyric acidemia (2M3HBA) is a rare condition. At least eleven people have been diagnosed with the condition, but the overall prevalence is currently unknown.

Also known as

  • 2M3HBA
  • HSD10 deficiency
  • 3H2MBD deficiency
  • 3-hydroxy-2-methylbutyryl-CoA dehydrogenase deficiency
  • Hydroxyacyl-CoA dehydrogenase II deficiency
  • 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency
  • MHBD deficiency

Follow-Up Testing

Your baby’s doctor may ask you if your baby is showing any of the signs of 2M3HBA (see Early Signs). If your baby has certain signs, your baby’s physician may suggest starting immediate treatment.

If your baby’s newborn screening result for 2-methyl-3-hydroxybutyric acidemia (2M3HBA) was out of the normal range, your baby’s doctor or the state screening program will contact you to arrange for your child to have additional testing. It is important to remember that an out-of-range screening result does not necessarily mean that your child has the condition. An out-of-range result may occur because the initial blood sample was too small or the test was performed too early. However, a few babies do have the condition, so it is very important that you go to your follow-up appointment for a confirmatory test. Because the harmful effects of untreated 2M3HBA can occur soon after birth, follow-up testing must be completed as soon as possible to determine whether or not your baby has the condition.

Follow-up testing will involve checking your baby’s urine and blood samples for harmful levels of acids and toxins. Certain acids and toxins build up in the body when a child has an organic acid condition, so studying the amounts of these substances in your baby’s body can help doctors determine if your child has a condition. High levels of C5-OH acylcarnitine in the blood and organic acids in the urine might be signs that your baby has 2M3HBA. In some cases, follow-up testing may also include testing a very small sample of skin.

About 2-Methyl-3-Hydroxybutyric Acidemia

Early Signs

Children with 2-methyl-3-hydroxybutyric acidemia (2M3HBA) start showing signs during infancy, typically between 9 and 14 months.

Males and females can have different signs of 2M3HBA. Males are more severely affected than females. Males might experience:

  • Difficulty with movements of their muscles
  • Loss of the developmental milestones met prior to age 5 (also known as regression)
  • Loss of motor skills

Females are less severely affected by 2M3HBA. Females affected by this condition may experience:

  • Mild developmental delays (but no regression)

Both males and females may experience:

  • Sleeping longer or more often
  • Tiredness
  • Loss of appetite
  • Weak muscle tone (also called hypotonia)
  • Epilepsy (seizures)

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

If your baby shows any of these signs, contact your baby’s doctor immediately.


Your baby will need a carefully planned diet to avoid the proteins that your baby’s body cannot break down. When your baby eats fats and proteins that he or she cannot break down, it may cause many of the signs mentioned in the Early Signs section. A metabolic doctor or a dietician can help you plan a well-balanced diet for your child.

Your baby will also need to eat often because long periods of time without food can trigger many of the signs mentioned in the Early Signs section. Illnesses and infections can also trigger these signs.

Expected Outcomes

Restricted diets have been effective for children who have been treated for 2-methyl-3-hydroxybutyric acidemia (2M3HBA), but we do not know what kinds of long-term effects this treatment could have.

Children with 2M3HBA may develop intellectual disabilities, even if they receive treatment. Males are at risk for severe intellectual disabilities, and females are at risk for mild intellectual disabilities.

To date, there have only been 11 documented cases of 2M3HBA, so the outcomes of this condition are not certain. Researchers are unsure about how the condition would progress without treatment. In other organic acid metabolism conditions, children who do not receive any treatment often develop permanent brain damage.


When we eat food, enzymes help break it down. Some enzymes break down proteins into their building blocks, amino acids. Other enzymes break down these amino acids further to their base molecules. In the disorder 2-methyl-3-hydroxybutyric acidemia (2M3HBA), the enzyme 2-methyl-3-hydroxybutyryl is not working correctly.

This enzyme’s job is to break down the amino acid isoleucine and some fats called branched-chain fatty acids. This enzyme is also involved with hormones. Hormones regulate the body’s activities, such as sexual development or nerve signals.

If your baby has 2M3HBA, their body is missing or making non-working 2-methyl-3-hydroxybutyryl-CoA dehydrogenase enzymes. When this enzyme is not working correctly, your baby’s body cannot break down isoleucine. This causes harmful substances to build up in your baby’s body and can be toxic.

2M3HBA is an X-linked dominant condition. This means that only one non-working copy of the gene is needed in order to have the condition. A male must inherit one non-working copy of the gene for 2M3HBA from his mother. A female can inherit the non-working gene from either her mother or her father. In X-linked conditions, the gene is carried on the X-chromosome, and males are affected more often than females. While having a child with 2M3HBA is rare, if one or both parents have the non-working gene for 2M3HBA, they can have more than one child with the condition. Learn more about X-linked dominant conditions.

Support for 2-Methyl-3-Hydroxybutyric Acidemia

Support Services

Support groups can help connect families who have a child or other family member affected with 2-methyl-3-hydroxybutyric acidemia (2M3HBA) with a supportive community of people who have experience and expertise in living with the condition. These organizations offer resources for families, affected individuals, health care providers, and advocates:

Accessing Care

Work with your baby’s doctor to determine the next steps for your baby’s care. Your baby’s physician may help you coordinate care with a doctor who specializes in metabolism, a dietician who can help plan your child’s specialized diet, or other medical resources in your community. Some children with 2-methyl-3-hydroxybutyric acidemia (2M3HBA) have developmental delays. If you think that your baby is not meeting their developmental milestones, ask your baby’s doctor about the next steps in accessing a developmental evaluation and care.

Because 2M3HBA is a genetic condition, you may want to talk with a genetics specialist. A genetic counselor or geneticist can help you understand the causes of the condition, discuss genetic testing for 2M3BA, and understand what this diagnosis means for other family members and future pregnancies. Speak with your baby’s doctor about getting a referral. The Clinic Services Search Engineoffered by the American College of Medical Genetics and Genomics and the Find a Genetic Counselor tool on the National Society of Genetic Counselors (NSGC) website are two good resources for you or your baby's health care provider to use to identify local specialists.

Families' Experiences

At this time we have not located a family story for this particular condition. If your family is affected by 2-methyl-3-hydroxybutyric acidemia (2M3HBA) and you would like to share your story, please contact us so other families may benefit from your experience.

Each family's experience with a condition is unique, but there are some parts of the evaluation and treatment of 2M3HBA that are similar to other organic acid conditions. You may find it useful to read the stories of families affected by other organic acid conditions. You can read these stories at the Organic Acidemia Association’s website.

References & Sources

Visit Medical Home Portal for more information on 2-methyl-3-hydroxybutyric acidemia (2M3HBA)

Visit Genetic and Rare Diseases Information Center (GARD) for more information on 2M3HBA

Visit MedlinePlus Genetics for more condition information

Visit the Organic Acidemia Association for condition information

Visit the Newborn Screening Coding and Terminology Guide by the U.S. Library of Medicine for condition information

ACT Sheets

Healthcare professionals can learn more about confirmatory testing by reading the American College of Medical Genetics and Genomics' Algorithm for Diagnosis and ACT Sheet, a guide for follow-up after newborn screening. You can visit this page of the ACMG website here.

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