Short/branched chain acyl-CoA dehydrogenase (SBCAD) deficiency (also known as 2-methylbutyryl-CoA dehydrogenase deficiency) is a rare disorder in which the body is unable to process proteins properly. Normally, the body breaks down proteins from food into smaller parts called amino acids. Amino acids can be further processed to provide energy for the body. People with SBCAD deficiency cannot process a particular amino acid called isoleucine.

Most cases of SBCAD deficiency are detected shortly after birth by newborn screening, which identifies abnormal levels of certain compounds in the blood. In individuals with this condition, a compound called 2-methylbutyryl carnitine is elevated in the blood and another called 2-methylbutyrylglycine is elevated in the urine (2-methylbutyrylglycinuria).

Most people with SBCAD deficiency have no health problems related to the disorder. A small percentage of affected individuals develop signs and symptoms of the condition, which can begin soon after birth or later in childhood. The initial symptoms often include poor feeding, lack of energy (lethargy), vomiting, and irritability. These symptoms sometimes progress to serious health problems such as difficulty breathing, seizures, and coma. Additional problems can include poor growth, vision impairment, learning disabilities, muscle weakness, and delays in motor skills such as standing and walking.

It is unclear why some people with SBCAD deficiency develop health problems and others do not. Doctors suggest that in some cases, signs and symptoms may be triggered by infections, prolonged periods without food (fasting), or an increased amount of protein-rich foods in the diet.

Mutations in the ACADSB gene cause SBCAD deficiency. This gene provides instructions for making an enzyme called short/branched chain acyl-CoA dehydrogenase (SBCAD), which performs a chemical reaction that helps process the amino acid isoleucine. Mutations in the ACADSB gene reduce or eliminate the activity of this enzyme. With a shortage (deficiency) of SBCAD activity, the body is unable to break down isoleucine properly. Researchers speculate that some features of this disorder, such as lethargy and muscle weakness, occur because isoleucine is not converted to energy. In addition, impairment of SBCAD may allow the buildup of toxic compounds, which can lead to serious health problems.

Normal Function

The ACADSB gene provides instructions for making an enzyme called short/branched chain acyl-CoA dehydrogenase (SBCAD, also known as 2-methylbutyryl-CoA dehydrogenase), which plays an important role in processing proteins. Normally, the body breaks down proteins from food into smaller parts called amino acids. Amino acids can be further processed to provide energy for the body. In cells throughout the body, SBCAD is found within specialized structures called mitochondria. Mitochondria convert energy from food into a form that cells can use.

The SBCAD enzyme helps break down a particular amino acid called isoleucine. Specifically, this enzyme helps with the third step of the process, performing a chemical reaction that converts a molecule called 2-methylbutyryl-CoA to another molecule, tiglyl-CoA. Additional chemical reactions convert tiglyl-CoA into molecules that are used for energy. Through similar chemical reactions, the SBCAD enzyme also aids in the breakdown of other amino acids.

Health Conditions Related to Genetic Changes

Short/branched chain acyl-CoA dehydrogenase deficiency

Researchers have identified more than 10 ACADSB gene mutations in people with short/branched chain acyl-CoA dehydrogenase (SBCAD) deficiency. While most people with this condition have no related health problems, some have reduced energy (lethargy), muscle weakness, seizures, developmental delays, or other health problems.

Many of the ACADSB gene mutations replace one of the amino acids in the SBCAD enzyme with an incorrect amino acid. Other mutations lead to an abnormally small version of this enzyme that is missing several amino acids. As a result of these mutations, SBCAD has little or no activity. With a shortage (deficiency) of normal enzyme activity, the body is unable to break down isoleucine properly. Researchers speculate that some features of this disorder, such as lethargy and muscle weakness, occur because isoleucine is not converted to energy. In addition, impairment of SBCAD may allow the buildup of toxic compounds, which can lead to serious health problems.

Other Names for This Gene

• 2-MEBCAD
• 2-methyl branched chain acyl-CoA dehydrogenase
• 2-methylbutyryl-CoA dehydrogenase
• ACAD7
• ACDSB_HUMAN
• acyl-CoA dehydrogenase, short/branched chain
• SBCAD
• short/branched chain acyl-CoA dehydrogenase

Genomic Location

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

• SBCAD deficiency is usually an autosomal recessive condition. Babies inherit the condition when each parent passes down a nonworking ACADSB gene to their baby. Only babies with two nonworking ACADSB genes—one from the mom and one from the dad—have this condition.
  • People with one working copy and one nonworking copy of the ACADSB 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 ACADSB gene, they have a 1 in 4 chance of having a child with SBCAD deficiency.
  • Carriers for SBCAD 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 SBCAD deficiency.
  • Parents who already have a child with SBCAD deficiency due to a change in the ACADSB gene still have a 1 in 4 chance of having another child with SBCAD 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.

Most babies with SBCAD deficiency do not have signs or symptoms.

A very small number of babies will have some health problems. In these babies, signs of the condition can appear anytime from a few months of age to childhood.

Signs of the condition may include the following:

• Poor appetite
• Sleeping longer or more often
• Tiredness
• Gets upset easily
• Vomiting
• Floppy arms and legs (hypotonia)
• Delayed growth
• Tight muscles (spasticity)
• Developmental delays

Newborn screening for SBCAD 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 SBCAD deficiency.

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

If your baby’s blood spot screening result for SBCAD 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.

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. Some more serious conditions, like Isovaleric Acidemia, can have similar results on the newborn screen. Follow-up is important for helping health care providers see if your baby has SBCAD deficiency or a different health condition.

False-positive newborn screening results for this condition are rare. Babies whose mothers took antibiotics with pivalic acid may also have false-positive results.

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. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps.

Most babies with SBCAD deficiency will not need treatment.

If your baby does have signs and symptoms of SBCAD deficiency, it is important to talk to your health care provider about which treatment(s), if any, your baby needs.

SBCAD deficiency is a rare condition; its worldwide prevalence is unknown. This condition is most common among Hmong populations in Southeast Asia and in people of Hmong descent, affecting 1 in 250 to 1 in 500 people in these communities. These individuals do not usually develop health problems related to the condition.