Inborn Errors of Metabolism

What are inborn errors of metabolism?

Inborn errors of metabolism (IEMs) are genetic disorders that impair metabolism – the multistep process by which our bodies turn the food we eat (carbohydrates, fats and proteins) into energy. When an enzyme needed for this process is missing or doesn't work correctly, an IEM condition results.

There are hundreds of IEM conditions, including:

• Hereditary fructose intolerance. The body lacks aldolase B, an enzyme needed to break down fructose (a sugar found in fruits, honey and certain sweeteners). In children with this condition, consuming foods with fructose can cause hypoglycemia (low blood sugar), nausea, vomiting and other symptoms. Ongoing fructose consumption may eventually damage the liver. Fortunately, most children do well with a fructose-free diet.
• Galactosemia. The body can't break down a sugar called galactose, which is present in lactose (a sugar found in all dairy products, including breast milk and dairy-milk-based infant formulas). To avoid damage to the brain, eyes, kidneys and liver, children with galactosemia must avoid dairy products and other foods with galactose for life.
• Maple syrup urine disease. The body can't break down three amino acids: isoleucine, leucine and valine. Children with maple syrup urine disease must follow a special diet that's low in these amino acids for life. The disorder was named for the characteristic smell it can cause in patients' urine.
• Phenylketonuria (PKU). The body lacks an enzyme needed to break down phenylalanine, an essential amino acid. (Essential amino acids are those the body can't produce and must obtain through foods.) People with PKU must follow a low-phenylalanine diet for life to prevent the amino acid from building up in their bodies and damaging the brain.

Inborn errors of metabolism are also known as inherited (or hereditary) metabolic disorders.

Symptoms of inborn errors of metabolism

Symptoms vary widely depending on the IEM's type and severity. They may involve any system in the body, with neurological and digestive symptoms being most common.

Neurological symptoms of IEMs include:

• Diminished energy
• Coma
• Seizures
• Developmental delay or regression
• Weakness and numbness in the hands and feet
• Poor muscle tone or lack of muscle control
• Psychiatric problems

Digestive system signs include:

• Recurrent episodes of vomiting
• Poor feeding and failure to thrive
• An enlarged liver or spleen
• Jaundice

Other symptoms include:

• Thickening or enlargement of the heart
• Certain facial or body features, such as deformed earlobes, a cleft palate, long face or lanky build
• Eye problems, such as cataracts
• Skin issues, such as rashes, hypopigmentation (areas of low melanin) or sun sensitivity
• Strange-smelling urine, breath, sweat or earwax

Diagnosis of inborn errors of metabolism

All U.S. states conduct newborn screening tests that check for several inborn errors of metabolism. For this routine test, a provider collects a few drops of blood from your baby's heel, usually on the second day of life. Because the test doesn't look for all IEMs and false negatives are possible, some cases aren't caught until later in childhood or even adulthood.

If an IEM is suspected later in childhood, the doctor will ask questions about your child's health history, family's health history, and factors that may have triggered their symptoms. The doctor may also examine your child for physical signs of an IEM and may order various blood, urine or genetic tests.

Treatment of inborn errors of metabolism

How doctors approach IEMs depends on the specific disorder. But in general, your child's treatment plan may include:

• Special diets. Some IEMs are managed with a modified diet. Children with phenylketonuria, for example, must follow a diet that's very low in phenylalanine to prevent the amino acid from building up in the body and damaging the nervous system. Children with hereditary fructose intolerance need to strictly avoid fructose and sucrose in their food and drinks.
• Enzyme replacement therapy. This treatment aims to supply the body with the missing or deficient metabolic enzyme. It's used for some lysosomal storage disorders, such as Gaucher disease.
• Medical foods. These are specially formulated foods and infant formulas designed to support the child's growth and development without using nutrients their body can't process.
• Medications. Certain medicines help the body get rid of excess substances that build up as a result of the metabolic error.

If your child has an IEM, they should receive care from a doctor who specializes in metabolic disorders.