Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency

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ORPHA:308410OMIM:614923E71.1
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Overview

Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase (BCKDK) deficiency is an extremely rare genetic metabolic condition. It is caused by mutations in the BCKDK gene, which plays a key role in regulating the breakdown of branched-chain amino acids (BCAAs) — leucine, isoleucine, and valine. When BCKDK is not working properly, the enzyme that breaks down these amino acids becomes overactive, leading to abnormally low levels of BCAAs in the blood. These amino acids are essential building blocks for brain development and function. Children with this condition typically develop autism spectrum disorder and epilepsy (seizures), along with intellectual disability. The low levels of branched-chain amino acids in the blood are a hallmark finding. Some children may also have low head size (microcephaly) and delays in motor and language development. The treatment approach centers on dietary supplementation with branched-chain amino acids to restore normal blood levels. Early diagnosis and treatment are important because BCAA supplementation has been shown to improve seizure control and may help with some behavioral and developmental symptoms. This condition is sometimes also referred to as BCKDK deficiency. Because it is so rare, management is best guided by specialists in metabolic diseases and neurology working together.

Key symptoms:

Autism spectrum disorder (difficulty with social interaction and communication)Epilepsy (recurrent seizures)Intellectual disabilitySpeech and language delaysMotor development delaysSmall head size (microcephaly)Low levels of branched-chain amino acids in the bloodBehavioral difficultiesLearning difficultiesRepetitive behaviors

Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Infantile

Begins in infancy, roughly 1 month to 2 years old

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency.

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No actively recruiting trials found for Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency at this time.

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No specialists are currently listed for Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency.

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Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

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Community

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Caregiver Resources

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Questions for your doctor

Bring these to your next appointment

  • Q1.What are my child's current branched-chain amino acid levels, and what is the target range?,How much BCAA supplementation does my child need, and how should it be given?,What type of seizures does my child have, and what is the best medication to control them?,How often should blood levels be monitored to adjust the supplement dose?,What therapies (speech, occupational, behavioral) do you recommend, and how often?,Are there any clinical trials or research studies my child could participate in?,Should other family members be tested for carrier status?

Common questions about Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency

What is Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency?

Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase (BCKDK) deficiency is an extremely rare genetic metabolic condition. It is caused by mutations in the BCKDK gene, which plays a key role in regulating the breakdown of branched-chain amino acids (BCAAs) — leucine, isoleucine, and valine. When BCKDK is not working properly, the enzyme that breaks down these amino acids becomes overactive, leading to abnormally low levels of BCAAs in the blood. These amino acids are essential building blocks for brain development and function. Children with this condition typically dev

How is Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency inherited?

Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency typically begin?

Typical onset of Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency is infantile. Age of onset can vary across affected individuals.