Conditions · Metabolism: amino acids and the urea cycle
Maple syrup urine disease !
In this disease leucine, isoleucine and valine are not broken down; they build up, harm the brain, and urine smells sweet, like maple syrup.
Updated 2026-11-01
Structures involved
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In biochemistry
- Branched-chain amino acid breakdown: Step 2 · Branched-chain α-ketoacid dehydrogenase complex (BCKDH)
- Branched-chain α-keto acid dehydrogenase (BCKDH)
- Glucogenic and ketogenic amino acids
- Newborn screening
- Chromatography
- Leucine
- Amino acids: structure, charge and pKa
What it is
An inherited organic acidaemia from lack of the branched-chain α-keto acid dehydrogenase complex (BCKDH).
Who gets it
It affects about 1 in 185,000 newborns worldwide; in the Old Order Mennonite population it reaches 1 in 380.
Causes
- Variants in BCKDHA, BCKDHB or DBT (autosomal recessive)
Risk factors
- Carrier parents
- Consanguinity
Pathophysiology
Branched-chain amino acids are transaminated, but their keto acids are not decarboxylated. Leucine and its keto acid build up, compete with other amino acids for entry into the brain and cause cerebral oedema, mainly in white matter and brainstem. Infections and fasting increase protein breakdown and trigger crises.
Classification
- Classic (severe neonatal)
- Intermediate
- Intermittent
- Thiamine-responsive
Symptoms and signs
- In the first days: poor feeding, vomiting and drowsiness
- Sweet odour of urine and earwax
- Abnormal movements and alternating hypotonia and hypertonia
- Seizures and coma
Diagnosis
- Clinical
- Neonatal encephalopathy with the typical odour; expanded newborn screening with high leucine.
- Tests
- Plasma amino acids with high leucine, isoleucine and valine and alloisoleucine present (diagnostic); urinary keto acids; genetic testing.
- Imaging
- Brain MRI: marked oedema of myelinated white matter, brainstem and cerebellum during crises.
Treatment
- Acute
- In a crisis: stop natural protein briefly, give high calories and a branched-chain-free formula; dialysis if leucine is very high
- Lifestyle
- Lifelong diet with a branched-chain-free formula and leucine monitoring
- Medical
- Thiamine in responsive forms
- Surgical
- Liver transplant, which provides enough enzyme for a nearly free diet
Complications
- Cerebral oedema and death in crises
- Intellectual disability
- Anxiety, depression and attention deficit
- Pancreatitis
Prognosis
Neonatal diagnosis and good metabolic control allow near-normal development; each severe crisis can leave sequelae.
Test yourself
Think of the answer, then tap the question to see it.
Which enzyme complex fails in this disease?
Branched-chain α-keto acid dehydrogenase (BCKDH), which decarboxylates the keto acids of leucine, isoleucine and valine.
Which of the accumulated amino acids is the most neurotoxic?
Leucine, which is measured to follow metabolic control.
Which plasma metabolite is diagnostic?
Alloisoleucine, which appears when branched-chain keto acids build up.
Related conditions
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Maple syrup urine disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); BCKDHA gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Branched-chain amino acid catabolism (Reactome, 2026).
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