Holocarboxylase synthetase deficiency is an inherited (genetic) condition that prevents the body from breaking down certain proteins, carbohydrates, and fats.

Holocarboxylase synthetase is an enzyme in your body that adds the vitamin biotin to other enzymes. Adding biotin helps those enzymes break down carbohydrates, proteins, and fats to use them for energy or get rid of them.

If your baby’s holocarboxylase synthetase enzyme is not working well, enzymes that need biotin do not work as well. This condition can be more or less severe depending on how well your baby’s holocarboxylase synthetase enzyme is working.

Breaking down proteins, carbohydrates, and fats for energy allows your body to work properly. When proteins, carbohydrates, and fats are not processed, waste and toxins can build up, and cause damage. If untreated, this damage leads to the signs and symptoms of the condition. In severe cases, this condition can result in brain damage or coma unless treated early.

Holocarboxylase synthetase deficiency is caused by a change in the HLCS gene. This gene gives the body instructions for making the enzyme, holocarboxylase synthetase. This enzyme attaches biotin to other enzymes needed to break down fats, proteins, and carbohydrates.

Without a working HLCS gene, your baby cannot make enough working enzyme. As a result, their body cannot properly break down fats, proteins, and carbohydrates to use them for energy and to get rid of waste.

Holocarboxylase synthetase deficiency is a genetic condition. Babies inherit it from their biological (birth) parents.

• Holocarboxylase synthetase deficiency is an autosomal recessive condition. Babies inherit the condition when each parent passes down a nonworking HLCS gene to their baby. Only babies with two nonworking HLCS genes—one from the mom and one from the dad—have this condition.
  • People with one working copy and one nonworking copy of the HLCS 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 HLCS gene, they have a 1 in 4 chance of having a child with holocarboxylase synthetase deficiency.
  • Carriers for holocarboxylase synthetase deficiency 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 holocarboxylase synthetase deficiency.
  • Parents who already have a child with holocarboxylase synthetase deficiency still have a 1 in 4 chance of having another child with holocarboxylase synthetase deficiency. This 1 in 4 chance stays the same for all future children.
• Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it.

Signs of holocarboxylase synthetase deficiency begin in infancy and often appear in the first few months of life.

Signs of the condition may include the following:

• Poor feeding
• Sleeping longer or more often (lethargy)
• Peeling skin rash
• Hair loss (alopecia)
• Vomiting
• Gets upset easily
• Floppy arms and legs (hypotonia)
• Breathing problems

Newborn screening for holocarboxylase synthetase deficiency is done using a small amount of blood collected from your baby’s heel. During screening, a special machine measures how much of certain substances (called acylcarnitines) are in your baby’s blood. Your body produces these substances when it breaks down food. Babies with high levels of these substances might have holocarboxylase synthetase deficiency.

What Happens After an Out-of-Range Screening Result?

If your baby’s blood spot screening result for holocarboxylase synthetase deficiency 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 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 out-of-range result for holocarboxylase synthetase deficiency because their mother has elevated acylcarnitine levels. These babies do not have and will not develop holocarboxylase synthetase deficiency. More testing on both mom and baby will determine who has high acylcarnitine levels.

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.

It is important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to prevent the health problems caused by this condition.

Treatments may include the following:

• Biotin supplements
• Careful management during illness

Children who receive early and ongoing treatment for holocarboxylase synthetase deficiency can have healthy growth and development.