Inborn Errors of Metabolism (IEM)

What are inborn errors of metabolism?

Inborn errors of metabolism, also known as inherited metabolic disorders or hereditary metabolic disorders, are a group of conditions that affect your ability to convert food into energy and remove waste and unhealthy substances from your body.

Your metabolism is a series of chemical processes that turn what you eat and drink into energy. Inborn errors of metabolism occur when your body isn’t able to complete these chemical processes as expected.

What are the types of inborn errors of metabolism?

There are hundreds of inborn errors of metabolism. Most conditions receive their names from the enzyme that isn’t working as it should. Some of the most common inborn errors of metabolism include:

• Lysosomal storage disorders: Your body isn’t able to remove or break down waste products, which causes toxins to build up in your body. Lysosomal storage disorders include Hurler syndrome, Gaucher disease and Tay-Sachs disease.
• Maple syrup urine disease: Amino acids build up in your body, which causes nerve damage and your urine (pee) to smell like maple syrup.
• Glycogen storage disease: Your body can’t store sugar from the food in your diet, which causes low blood sugar.
• Mitochondrial diseases: Cells in your body aren’t able to produce enough energy from the food you eat. This condition affects the function of many organ systems, including your brain, muscles, liver, kidneys, etc.
• Peroxisomal disorder: Similar to lysosomal storage disorder, peroxisomal disorder leads to toxins building up in your body.
• Metal metabolism disorders: Your body contains small traces of metals and those metals build up to toxic levels that are harmful to your body. These include Wilson disease (excess copper levels) and hemochromatosis (excess iron levels).
• Urea cycle disorder: Your body isn’t able to process ammonia and it builds up to toxic levels in your blood.

Who do inborn errors of metabolism affect?

Inborn errors of metabolism (IEM) can affect anyone because the condition is the result of a genetic change in your DNA. Each type of IEM has a different form of inheritance and you’re at a higher risk of having an IEM if someone in your family has the condition.

How common are inborn errors of metabolism?

Inborn errors of metabolism affect an estimated 1 out of every 2,500 births worldwide.

How do inborn errors of metabolism affect my body?

Inborn errors of metabolism affect your body’s ability to process one of the following from the foods or beverages you eat or drink, including:

• Carbohydrates.
• Sugar.
• Protein.
• Fat.

As a result, symptoms of the condition affect multiple organs and systems within your body that cause changes to your development, growth and your ability to interact with the world around you.

What are the symptoms of inborn errors of metabolism?

Symptoms of common inborn errors of metabolism include:

• Developmental delays.
• Weight loss.
• Growth challenges.
• Seizures.
• Poor appetite.
• Low energy (lethargic).
• Unusual odors of urine, sweat or breath.
• Abdominal pain.

The symptoms of inherited metabolic disorders vary depending on the condition. Symptoms range from mild to severe and can be life-threatening if left untreated.

What causes inborn errors of metabolism?

A genetic mutation that happens when your cells divide and replicate during fetal development causes inborn errors of metabolism (IEM).

Several possible genes cause each type of IEM. Certain genes in your body provide instructions for proteins to perform chemical reactions in your metabolism after you eat. Special proteins called enzymes produce these chemical reactions.

When you have an inborn error of metabolism, your enzymes don’t have the instructions they need to do their job within your metabolism, which causes symptoms of the specific IEM that affects your body.

How are inborn errors of metabolism diagnosed?

Your provider will diagnose inborn errors of metabolism either before your child is born or shortly after birth through a routine physical exam or screening. Some people receive a diagnosis later during adulthood when symptoms become apparent.

What screening tests diagnose inborn errors of metabolism?

Your provider will diagnose inborn errors of metabolism (IEM) with screening tests. Screening tests include a blood test or a urine test and a physical exam. Since there are so many different types of IEM, screening tests to diagnose an IEM could include:

• Metabolic testing: This test looks at the amino acid (basic building block of proteins), fat and glucose metabolism patterns to help narrow down the diagnosis. This test can be a urine or blood test.
• Genetic testing: Your provider will remove a small sample of your blood or take a swab of the saliva inside of your mouth to examine changes in your genes.
• Amniocentesis: During pregnancy, your provider will remove a small sample of amniotic fluid (the fluid surrounding the fetus) to examine it for genetic changes.
• Glucose testing: Your provider will check your blood glucose (sugar) level by removing a small sample of your blood. This test often happens if you have symptoms of lethargy, low energy or seizures.
• Eye exam: Some IEMs affect your vision. An eye exam will test your ability to see clearly and also check for conditions that affect your eyes.

How are inborn errors of metabolism treated?

Treatment for inborn errors of metabolism varies based on the type but could include:

• Changing your diet: Since your body has trouble processing foods and beverages, removing certain food items from your diet can prevent flares of symptoms.
• Taking medicine: Your provider might recommend taking certain medicines that can help your metabolism function as expected. Drugs could include enzyme or chemical replacements.
• Undergoing dialysis: A procedure that removes toxins out of your blood.
• Organ transplant: To treat severe cases of IEM, a liver transplant might be necessary.

What medications treat inborn errors of metabolism?

Your provider might recommend taking certain medicines to treat inborn errors of metabolism (IEM). The medicine will vary based on the type of IEM and could include:

• Glucose solution.
• Insulin.
• Sodium benzoate or sodium phenylacetate.
• Amino acid supplements.
• Enzyme replacement.
• Dietary supplements.

Are there side effects of inborn errors of metabolism?

Inborn errors of metabolism can be harmful to your body if you’re unable to process certain food products in your metabolism. This could cause toxic substances to build up in your blood and cause:

• Seizures.
• Organ failure.
• Brain damage.

How do I manage symptoms of inborn errors of metabolism?

Inborn errors of metabolism can cause you to feel tired and lethargic. You might not have the energy to do normal activities during a flare of symptoms. It’s important to follow your provider’s treatment plan to make sure you’re eating and drinking food products that are safe for your body to process.

It can be difficult to apply your provider’s recommended treatment plan, especially if it involves restrictive eating. Talk to your provider or a nutritionist to help you navigate your new diet plan and adopt these changes to your normal routine.

How can I prevent inborn errors of metabolism?

You can’t prevent inborn errors of metabolism because they’re the result of genetic changes. If you plan on expanding your family, talk to your provider about genetic testing to learn more about the risks of having a child with a genetic condition.

What can I expect if I have inborn errors of metabolism?

There isn’t a cure for inborn errors of metabolism (IEM). Your outlook varies based on the severity of your symptoms. Some cases of IEM can be very dangerous if you have high levels of toxic material in your body that your body can’t get rid of on its own. Most people diagnosed with the condition have a normal lifespan with early detection and treatment, along with lifelong lifestyle changes.

When should I see my healthcare provider?

Visit your healthcare provider if you have a flare of symptoms that don’t resolve with your provider’s recommended treatment plan. If you’re pregnant, ask your provider about prenatal and newborn screenings for your baby to identify inborn errors of metabolism.

If you have a seizure, call 911 (or your local emergency service number) or visit the emergency room immediately.

What questions should I ask my doctor?

If you have an inherited metabolic disorder, you may want to ask your provider:

• What kind of inherited metabolic disorder do I have?
• What’s the outlook for this disorder?
• What does my treatment involve?
• Are there complications I should look out for?
• How will it affect my daily life?
• Is there a support group where I can find other people with this rare condition?

Who discovered inborn errors of metabolism?

Medical history names Archibald Garrod the founder of inborn errors of metabolism in 1908. His research suggested that inborn errors of metabolism connect to genetic changes.