Find A Condition

3-Hydroxy-3-methylglutaric aciduria

Print
Also known as:
  • HMG
  • 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
  • HMG-CoA lysase deficiency
  • deficiency of hydroxymethylglutaryl-CoA lyase
  • 3HMG
  • 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency
  • hydroxymethylglutaric aciduria
  • 3-OH 3-CH3 glutaric aciduria

3-hydroxy-3-methylglutaric aciduria (HMG) is a condition in which the body is unable to break down certain proteins. People with the condition are also unable to produce ketone bodies, substances that help the body store energy.  HMG is considered an organic acid condition because it can lead to a harmful amount of organic acids and toxins in the body.  Early detection and treatment can often prevent the serious outcomes of this condition.

Follow-Up Testing

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

If your baby’s newborn screening result for 3-hydroxy-3-methylglutaric aciduria (HMG) 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 HMG can occur within days after birth, follow-up testing must be conducted as soon as possible to determine whether or not your child 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 he or she has a condition. High levels of C5-OH acylcarnitines in the blood or organic acids in the urine can be signs of HMG. Sometimes follow-up testing may also include testing a very small sample of skin.

 


About 3-Hydroxy-3-methylglutaric aciduria

Early Signs

Each child with 3-hydroxy-3-methylglutaric aciduria (HMG) has a slightly different experience. Most affected children start to show signs of HMG between 3 months and 2 years of age.  In a few cases, babies start to show signs of the condition just a few days after birth.

Signs of HMG include:

  • Poor appetite
  • Sleeping longer or more often
  • Tiredness
  • Irritability
  • Weak muscle tone (known as hypotonia)
  • Fever
  • Vomiting
  • Diarrhea
  • Low blood sugar (hypoglycemia)
  • Behavior changes

Many of these signs may 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.i

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

Treatment
Dietary Treatment

Your baby will need to be on a strict diet to avoid certain proteins and fats. 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’s doctor might recommend special baby formulas and foods made especially for children with 3-hydroxy-3-methylglutaric aciduria (HMG). These formulas will likely be needed through adulthood.

Your baby will also need to eat often. Long periods of time without food, illnesses, and infections can trigger signs of HMG.

Supplements and Medication

Your baby’s doctor might write a prescription for L-carnitine supplements. L-carnitine is a naturally occurring substance in the body, but your baby’s body might not make enough of it. Prescription L-carnitine supplements can help get rid of toxic waste products in the body.

Expected Outcomes

If your baby receives early and careful treatment, he or she will most likely have a healthy life with normal growth and development.

It is possible, even with treatment, for babies with 3-hydroxy-3-methylglutaric aciduria (HMG) to have low blood sugar and other signs of HMG.

Early screening and treatment are very important. Babies who do not receive treatment usually die or develop permanent brain damage.

Causes

When we eat food, enzymes help break it down. Some enzymes help break down protein into its building blocks (called amino acids). In 3-hydroxy-3-methylglutaric aciduria (HMG), the enzyme “HMG CoA lyase” is not working correctly.

This enzyme has two jobs. First, it breaks down leucine, an amino acid, to make energy. Second, it helps make ketone bodies from fat. Ketone bodies are substances used for energy. 

When this enzyme doesn’t work,  organic acids build up in the body which can be harmful in large amounts. Generally, if your body starts to run low on the ketone bodies needed for your brain, you can use stored fat from other areas to make the ketone bodies. If there is not enough sugar in your body (such as between meals) then your body is unable to turn the fat into the needed ketone bodies and you may begin to experience symptoms.

HMG is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for HMG, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with HMG is rare, when both parents are carriers, they can have more than one child with the condition. Learn more about autosomal recessive inheritance.


Support for 3-Hydroxy-3-methylglutaric aciduria

Support Services

Support groups can help connect families who have a child or other family member affected with 3-hydroxy-3-methylglutaric aciduria 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 child’s care.  Your baby’s doctor may help you coordinate care with a doctor specializing in metabolism, a dietician who can help plan your child’s specialized diet, or other medical resources in your community.  Some children with 3-hydroxy-3-methylglutaric aciduria (HMG) have developmental delays.  If you think that your baby is not meeting his or her developmental milestones, ask your baby’s health care provider about the next steps in accessing a developmental evaluation and care.

Because HMG 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 HMG, 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 Engine offered by the National Coordinating Center for the Regional Genetic and Newborn Screening Service Collaboratives and the Find a Genetic Counselor tool on the National Society of Genetic Counselors 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 3-hydroxy-3-methylglutaric aciduria (HMG) 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 HMG 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.


States Screening for 3-Hydroxy-3-methylglutaric aciduria

Back to the Top