What's maple syrup urine disease?
Maple syrup urine disease is an inherited metabolic disorder in which the branched-chain alpha-ketoacid dehydrogenase (BCKDH) enzyme complex cannot break down the branched-chain amino acids leucine, isoleucine, and valine. These build up and become toxic, producing recurrent metabolic crises and the characteristic sweet, maple-syrup smell of the urine. It is autosomal recessive and can stem from variants in any of three genes (BCKDHA, BCKDHB, DBT); this entry confirms BCKDHA, the E1-alpha subunit, as the principal driver. It is managed with a strict branched-chain-amino-acid-restricted diet or liver transplant.
| Also indexed as | ORPHA:511, MONDO:0009563 |
|---|---|
| Features mapped | 13 |
| Treatments mapped | 5 |
| Published sources | 17 |
| Last reviewed | 2026-08-04 |
Signs and symptoms
Cerebral edema
During a metabolic crisis, dangerous swelling of the brain (cerebral edema) can develop and is a leading cause of death in maple syrup urine disease.
Elevated circulating L-alloisoleucine concentration
A specific amino acid, allo-isoleucine, builds up in the blood in maple syrup urine disease. It is the disease's signature marker and is not normally found in people without the condition.
Ketosis
Buildup of branched-chain amino acids and their byproducts produces ketosis during episodes of metabolic decompensation in maple syrup urine disease.
Elevated circulating branched chain amino acid concentration
Because the enzyme that should break them down is missing or weak, the three branched-chain amino acids (leucine, isoleucine, and valine) build up to toxic levels in the blood. This buildup is the core problem in maple syrup urine disease.
Seizure
Seizures can occur in maple syrup urine disease, especially in newborns when the toxic amino acids build up; in one large case review just over half of the babies had seizures.
Lethargy
Increasing lethargy and poor responsiveness in the first days or weeks of life can signal a metabolic crisis in maple syrup urine disease.
Coma
During a metabolic crisis, rising toxic amino acids can cause lethargy, encephalopathy, and coma, which can be life-threatening without urgent treatment.
Autosomal recessive inheritance
Maple syrup urine disease is inherited in an autosomal recessive pattern: both inherited gene copies must carry disease variants for a child to be affected.
Feeding difficulties in infancy
Trouble feeding in the newborn period is one of the typical early signs of the classic form of maple syrup urine disease.
Vomiting
Poor feeding and vomiting are common early signs in a newborn with maple syrup urine disease as toxic byproducts accumulate.
Global developmental delay
Delays in reaching developmental milestones are part of the classic newborn presentation of maple syrup urine disease, and untreated the disease can cause lasting damage to the brain and nervous system.
Respiratory insufficiency
When the disease is severe and untreated, breathing can fail, sometimes requiring a breathing machine. In one large case review about a quarter of affected newborns developed respiratory failure.
Maple syrup odor
A sweet, maple-syrup smell in the earwax and urine is a classic early sign of the disease, and it gives maple syrup urine disease its name.
How it is diagnosed
Maple syrup urine disease
Diagnosed using: plasma branched-chain amino acids and newborn screening (leucine, alloisoleucine).
“Suspected patients should have blood or urine branched-chain amino acid levels tested and brain MRI as early as possible to enable early…”
Maple syrup urine disease
Diagnosed using: plasma alloisoleucine (pathognomonic marker).
“The diagnosis of MSUD is based on elevated BCAAs and allo-isoleucine in plasma, and branched-chain hydroxyacids and ketoacids in urine. The identification of alloisoleucine >5 µmol/L is considered pathognomonic.”
Maple syrup urine disease
Diagnosed using: urine organic acids (branched-chain hydroxyacids and ketoacids).
“The diagnosis of MSUD is based on elevated BCAAs and allo-isoleucine in plasma, and branched-chain hydroxyacids and ketoacids in urine.”
Maple syrup urine disease
Diagnosed using: genetic testing (BCKDHA, BCKDHB, DBT sequencing).
“These findings emphasize the value of genetic testing for early diagnosis and genetic counseling in consanguineous populations, with implications for managing MSUD and preventing complications.”
Treatment and management
What the research describes, not a recommendation. Treatment decisions belong with your clinician.
This covers treatments that appear in the published research mapped here. Investigational and experimental therapies are not included, so their absence is a boundary of this map, not a sign they do not exist.
liver transplantation
Liver transplantation can treat the classic, severe form of maple syrup urine disease, supplying enough working enzyme that many people can return to a normal, unrestricted protein diet.
Used to help with: Maple syrup urine disease.
“…allogeneic liver…”
branched-chain amino acid restricted diet
In maple syrup urine disease, calories are kept high to stop the body from breaking down its own protein, which would otherwise release more of the branched-chain amino acids that build up to toxic levels.
Used to help with: Maple syrup urine disease.
“…an exacting prescription…”
thiamine supplementation
Maple syrup urine disease comes in several forms, and one of them, the thiamine-responsive type, improves with thiamine (vitamin B1) supplementation. Most people with the disease have the classic form, which does not respond to thiamine.
Used to help with: Maple syrup urine disease.
“Maple syrup urine disease (MSUD) is a rare inborn error of the branched chain amino acid metabolism, which can be classified as classical, intermediate, intermittent, and thiamine responsive types.”
sick-day and emergency management of metabolic decompensation
When someone with maple syrup urine disease becomes ill, the body starts breaking down its own protein, which can push the toxic amino acids dangerously high. Management aims to reverse this: at home, taking in extra carbohydrate for calories; in hospital, intravenous sugar (dextrose) and fat (lipid) with daily amino-acid monitoring.
Used to help with: Maple syrup urine disease.
“Illness: a) home illness management: increased carbohydrate intake b) illness management at hospital: intravenous dextrose, intravenous lipid and daily plasma amino acid…”
hemodialysis for acute metabolic crisis
During a severe metabolic crisis in maple syrup urine disease, when the toxic amino acids climb very high, hemodialysis can be used to clear them from the blood. In emergency-department studies this was needed more often during acute decompensation than during stable visits.
Used to help with: Maple syrup urine disease.
“AMD visits were associated with worse clinical outcomes, including higher rates of pediatric intensive care admissions (22% vs. 2.6%) and increased hemodialysis requirements (19% vs. 1.6%).”
What changes how it shows up
Carrying the genetic change is not the whole story. The factors below are described in the research mapped here as changing whether, or how strongly, the condition appears. They modulate how the genotype is expressed; they do not, on their own, cause or cure it.
BCKDH gene complex (BCKDHA, BCKDHB, DBT)
Maple syrup urine disease is caused by changes in the genes that build the branched-chain alpha-keto acid dehydrogenase complex; variants can occur in the BCKDHA, BCKDHB, or DBT gene.
Described as modulating: Maple syrup urine disease.
“…novel mutations in the BCKDHA, BCKDHB, and DBT…”
autosomal recessive inheritance
Maple syrup urine disease is inherited in an autosomal recessive pattern, meaning both inherited copies of the responsible gene must carry a disease-causing change.
Described as modulating: Maple syrup urine disease.
“Maple syrup urine disease (MSUD) is an autosomal recessive inborn error of branched-chain amino acid metabolism caused by an inherited deficiency of branched-chain alpha-ketoacid dehydrogenase (BCKDH) activity that degrades isoleucine, leucine, and valine.”
How to read the evidence labels
Where this comes from
This guide is built from 17 published source(s). Every claim above links back to one of them. Click any source ID to read the original on PubMed.
Take it further
Printed, source-linked documents built from this condition's graph — ready to bring to an appointment or attach to a coverage request. Every claim carries its published source, the same as this guide.