GENE GUIDE

BCKDK-Related Syndrome

This guide is not meant to take the place of medical advice. Please consult with your doctor about your genetic results and health care choices. This Gene Guide was last updated in 2025. As new information comes to light with new research we will update this page. You may find it helpful to share this guide with friends and family members or doctors and teachers of the person who has BCKDK-Related Syndrome.
a doctor sees a patient

BCKDK-related syndrome is also called branched-chain keto acid dehydrogenase kinase deficiency. For this webpage, we will be using the name BCKDK-related syndrome to encompass the wide range of variants observed in the people identified.

BCKDK-related syndrome happens when there are changes in the BCKDK gene. These changes can keep the gene from working as it should.

Key Role

The BCKDK gene is important for mitochondria, which produce the energy that cells need to do work. This gene is also important for processing some amino acids in the body, which helps cells to function properly.

Symptoms

Because the BCKDK gene is important for brain activity, many people who have BCKDK-related syndrome have:

  • Developmental delay
  • Intellectual disability
  • Autism
  • Motor issues
  • Seizures
  • Language issues
  • Behavioral issues

BCKDK-related syndrome is a genetic condition, which means that it is caused by variants in genes. Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the BCKDK gene: one copy from their mother’s egg, and one copy from their father’s sperm. 

Some people have variants to their genes that prevent them from working properly. A variant in one copy of the BCKDK gene has little or no effect on their health — because one working copy is enough. People who have one working copy of the gene and one non-working copy of the gene are called ‘carriers’. Some people have genes where both copies do not work as they should. In these cases, the person has inherited non-working copies of the gene from both parents. This can lead to physical issues, developmental issues, or both.

Autosomal recessive conditions

BCKDK-related syndrome can also be an autosomal recessive genetic condition. To be affected with symptoms of an autosomal recessive genetic condition, a person has two damaging variants on both copies of their BCKDK. For someone with an autosomal recessive genetic syndrome, every time they have a child they will pass on one non-working copy of BCKDK.

Autosomal Recessive Genetic Syndrome

GENE / gene
Carrier
father
GENE / gene
Carrier
mother
gene / gene
Non-carrier child
GENE / gene
Carrier of the variant
GENE / gene
Carrier of the variant
GENE / GENE
Child with autosomal recessive condition

Why does my child have a change in the BCKDK gene?

No parent causes their child’s BCKDK-related syndrome. We know this because no parent has any control over the gene changes that they do or do not pass on to their children. Please keep in mind that nothing a parent does before or during the pregnancy causes this to happen. The gene change takes place on its own and cannot be foreseen or stopped.

Each family is different. A geneticist or genetic counselor can give you advice on the chance that this will happen again in your family.

  • The risk of the same biological parents to a child with an autosomal recessive genetic condition, having another child who has BCKDK-related syndrome is almost always 25 percent.
  • The chance of two carrier parents having a child who is also a carrier is 50 percent. Carriers are not expected to have symptoms.
  • The chance of them having a child who is not a carrier at all is 25 percent.

For a person who has BCKDK-related syndrome, the risk of having a child who has the same syndrome depends on their partner.

  • If their partner is a carrier, they have a 50 percent chance of having a child who has the syndrome and a 50 percent chance of having a child who is a carrier.
  • If their partner is not a carrier, they have nearly a 0 percent chance of having a child who has the syndrome and a 100 percent chance of having a child who is a carrier.

As of 2024, at least 27 people with BCKDK-related syndrome have been described in medical research.

Most people who have a BCKDK-related syndrome do not look very different. Some people have a small head size.

Scientists and doctors have only just begun to study BCKDK-related syndrome. At this point, there are no medicines designed to treat the syndrome. A genetic diagnosis can help people decide on the best way to track the condition and manage therapies. Doctors can refer people to specialists for:

  • Physical exams and brain studies
  • Genetics consults
  • Development and behavior studies
  • Other issues, as needed

A developmental pediatrician, neurologist, or psychologist can follow progress over time and can help:

  • Suggest the right therapies. This can include physical, occupational, speech, or behavioral therapy.
  • Guide individualized education plans (IEPs).

Specialists advise that therapies for BCKDK-related syndrome should begin as early as possible, ideally before a child begins school.

If seizures happen, consult a neurologist. There are many types of seizures, and not all types are easy to spot. To learn more, you can refer to resources such as the Epilepsy Foundation’s website: epilepsy.com/learn/types-seizures.

This section includes a summary of information from major published articles. It highlights how many people have different symptoms. To learn more about the articles, see the Sources and References section of this guide.

Learning

People with BCKDK-related syndrome had developmental delays or intellectual disabilities, and speech issues. Most people had severe intellectual disabilities, and some people had a developmental regression of motor and/or language skills.

  • 18 out of 18 people had developmental delays or intellectual disabilities (100 percent)
  • 17 out of 17 people had speech issues (100 percent)
  • 5 out of 8 people had developmental regression (63 percent)

Behavior

Almost all people with BCKDK-related syndrome had behavioral challenges, such as features of autism, autism, aggression, self-injury, hyperactivity, and attention-deficit/hyperactivity disorder (ADHD).

  • 20 out of 21 people had behavioral challenges (95 percent)
  • 17 out of 23 people had features of autism (74 percent)
  • 11 out of 19 people had autism (58 percent)
  • 8 out of 18 people had aggression (44 percent)
  • 5 out of 17 people had self-injury (29 percent)
  • 5 out of 21 people had hyperactivity (24 percent)
  • 4 out of 18 people had ADHD (22 percent)

Brain

Some people with BCKDK-related syndrome had neurological issues, such as lower than average muscle tone (hypotonia) and seizures.

  • 5 out of 17 people had hypotonia (29 percent)
  • 15 out of 26 people had seizures (58 percent)
Human head showing brain outline
29%
5 out of 17 people had hypotonia.
58%
15 out of 26 people had seizures.

Mobility

Few people with BCKDK-related syndrome had abnormal movements, such as dystonia, ataxia, and clumsiness.

  • 3 out of 20 people had abnormal movements (15 percent)
  • 2 out of 10 people had dystonia (20 percent)
  • 1 out of 20 people had ataxia (5 percent)
  • 12 out of 15 people had clumsiness (80 percent)
15%
3 out of 20 people had abnormal movements.
20%
2 out of 10 people had dystonia.
5%
1 out of 20 people had ataxia.
80%
12 out of 15 people had clumsiness.

Other medical features

People with BCKDK-related syndrome had feeding difficulties and hearing impairment.

  • 5 out of 20 people had feeding difficulties (25 percent)
  • 3 out of 21 people had hearing impairment (14 percent)

Where can I find support and resources?

Simons Searchlight

Simons Searchlight is an online international research program, building an ever growing natural history database, biorepository, and resource network of over 175 rare genetic neurodevelopmental disorders. By joining their community and sharing your experiences, you contribute to a growing database used by scientists worldwide to advance the understanding of your genetic condition. Through online surveys and optional blood sample collection, they gather valuable information to improve lives and drive scientific progress. Families like yours are the key to making meaningful progress. To register for Simons Searchlight, go to the Simons Searchlight website at www.simonssearchlight.org and click “Join Us.”

Sources and References

The content in this guide comes from published studies about BCKDK-related syndrome.

  • Boemer, F., Josse, C., Luis, G., Di Valentin, E., Thiry, J., Cello, C., Caberg, J. H., Dadoumont, C., Harvengt, J., … & Debray, F. G. (2022). Novel loss of function variant in BCKDK causes a treatable developmental and epileptic encephalopathy. International Journal of Molecular Sciences, 23(4), 2253. https://pmc.ncbi.nlm.nih.gov/articles/PMC8878489/
  • Paracha, S. A., Nawaz, S., Tahir Sarwar, M., Shaheen, A., Zaman, G., Ahmed, J., Shah, F., Khwaja, S., Jan, A., … & Ansar, M. (2024). The genetic cause of neurodevelopmental disorders in 30 consanguineous families. Frontiers in Medicine (Lausanne), 11, 1424753. https://pmc.ncbi.nlm.nih.gov/articles/PMC11392838/
  • Tangeraas, T., Constante, J. R., Backe, P. H., Oyarzábal, A., Neugebauer, J., Weinhold, N., Boemer, F., Debray, F. G., Ozturk-Hism, B., … & García-Cazorla, A. (2023). BCKDK deficiency: A treatable neurodevelopmental disease amenable to newborn screening. Brain, 146(7), 3003-3013. https://pubmed.ncbi.nlm.nih.gov/36729635/

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