BCKDHB (Branched Chain Keto Acid Dehydrogenase E1 Beta)

Overview

BCKDHB encodes the beta subunit of the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, an enzyme responsible for breaking down the branched-chain amino acids leucine, isoleucine, and valine. Mutations lead to Maple Syrup Urine Disease (MSUD), a potentially life-threatening metabolic disorder.

📍 Chromosomal Position

6q14.1 (Chromosome 6)

🧬 Gene Category

Hereditary Diseases / Metabolism

🔬 Inheritance

Autosomal recessive

📊 Prevalence

~1:185,000 (higher in certain populations)

Function & Significance

The BCKDH enzyme is a multi-enzyme complex located in the mitochondria that catalyzes the second step in the breakdown of branched-chain amino acids (BCAAs). These amino acids come from dietary protein and must be degraded to avoid toxic accumulation.

In mutations in BCKDHB (or other subunits of the complex), this breakdown is blocked. BCAAs and their keto acids accumulate in the blood and urine, leading to severe neurological damage, metabolic acidosis, and the characteristic sweet smell of the urine (hence the name “Maple Syrup Urine Disease”).

🔬 Branched-Chain Amino Acids

Leucine, isoleucine, and valine are essential amino acids that the body cannot produce itself. They are important for muscle building and energy metabolism. In MSUD, they must be strictly limited, requiring a lifelong specialized diet.

Associated Diseases

🍁 Maple Syrup Urine Disease (MSUD)

Classical form with neonatal encephalopathy, sweet urine odor, seizures
🧠 Neurological Damage

Untreated MSUD leads to irreversible brain damage and intellectual disability
⚡ Metabolic Crises

Acute decompensation during infections or increased protein intake

🧬 Relevant SNPs

rs121907988
6:80162380

Allele 1

Allele 2

Significance: Tyr393Asn (Y393N) – Pathogenic missense mutation that severely reduces enzyme activity. Homozygous carriers develop the classical form of Maple Syrup Urine Disease.

⚕️ Clinical Significance

MSUD is included in newborn screening in many countries. Early diagnosis is life-saving, as a protein-reduced diet must be started immediately. Untreated, the disease leads to severe neurological damage or death within a few weeks.

Therapy: Lifelong low-protein diet with special amino acid mixtures free of leucine, isoleucine, and valine. Intensive medical treatment is required during metabolic crises. Liver transplantation can be curative in severe cases.

📚 Data Sources

The information on this page is based on the following scientific sources:

OMIM: #248600 (Maple Syrup Urine Disease, Type Ib)
dbSNP: rs121907988
ClinVar: Pathogenic BCKDHB variants
PubMed: Literature on MSUD and amino acid metabolism
Orphanet: ORPHA268145 (Classic maple syrup urine disease)

Last update: February 2026

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BCKDHB