Organic Acidurias and Maple Syrup Urine Disease
On this page
Direct answer
Organic acidurias and maple syrup urine disease are inborn errors of amino acid breakdown that cause ketoacidosis and often hyperammonaemia in infancy. Maple syrup urine disease results from deficiency of the branched chain alpha-ketoacid dehydrogenase complex, so leucine, isoleucine and valine accumulate and give the urine its characteristic smell. Acute care stops protein intake, gives calories, corrects acidosis and removes toxic metabolites, with lifelong dietary restriction afterwards.
What you must remember
- Odour clues: maple syrup smell in urine, sweat and earwax in MSUD; a sweaty feet odour in isovaleric acidaemia, from isovaleric acid.
- MSUD enzyme: the branched chain ketoacid dehydrogenase complex needs thiamine pyrophosphate, and a thiamine-responsive variant exists in a minority.
- Propionic acidaemia: propionyl-CoA carboxylase deficiency, a biotin-dependent enzyme; L-carnitine supplementation is used to handle the toxic propionyl-CoA.
- Methylmalonic acidaemia: methylmalonyl-CoA mutase or cobalamin defects, with hydroxocobalamin-responsive variants in some patients.
- Acute presentation: vomiting, lethargy, poor feeding, seizures and metabolic acidosis with a raised anion gap, usually after protein intake begins.
- Key investigations: urine organic acids by gas chromatography-mass spectrometry, plasma amino acids, and raised alloisoleucine in plasma as a specific marker of MSUD.
- Acute management: stop protein, give IV glucose and insulin where needed, correct acidosis, and use dialysis for severe or refractory hyperammonaemia.
Comparing the branched chain and organic acid defects
Each disorder is paired with its enzyme and its most useful laboratory clue in an infant with unexplained acidosis. The odour narrows the list, but enzyme assay or urine testing confirms the diagnosis, and isovaleric acidaemia is easily missed without urine organic acids.
| Disorder | Enzyme or defect | Odour | Key clue |
|---|---|---|---|
| Maple syrup urine disease | Branched chain ketoacid dehydrogenase | Maple syrup | Alloisoleucine in plasma |
| Propionic acidaemia | Propionyl-CoA carboxylase | Not classic | Raised propionylcarnitine |
| Methylmalonic acidaemia | Methylmalonyl-CoA mutase or cobalamin | Not classic | Methylmalonic acid in urine |
| Isovaleric acidaemia | Isovaleryl-CoA dehydrogenase | Sweaty feet | Isovalerylglycine in urine |
Propionic and methylmalonic acidaemia share a raised propionylcarnitine on blood acylcarnitine profiling, so urine organic acids separate them. MSUD is distinguished by its amino acid pattern rather than by an acylcarnitine clue. Samples for organic acids and amino acids should be taken before protein is stopped, since fasting and treatment can alter the pattern and blur the diagnosis.
Where the exam tests these disorders
Examiners pair each disorder with its odour, its enzyme and the first step in acute care.
- Trap: attributing neonatal hyperammonaemia with acidosis to a urea cycle defect without checking organic acids. Correct: propionic and methylmalonic acidaemia also raise ammonia, so urine organic acids and an acylcarnitine profile are needed to tell them apart.
- Trap: resuming a normal protein diet once the acute crisis settles in MSUD. Correct: branched chain amino acid restriction is maintained long-term, guided by plasma leucine and other amino acid levels.
- Trap: calling the odour a diagnosis on its own. Correct: the odour narrows the list, but enzyme assay or urine organic acid analysis confirms the disorder.
Frequently asked questions
What causes maple syrup urine disease?
Maple syrup urine disease is caused by deficiency of the branched chain alpha-ketoacid dehydrogenase complex. Leucine, isoleucine and valine therefore accumulate in blood and urine, which gives the characteristic maple syrup odour.
Which odour is associated with isovaleric acidaemia?
Isovaleric acidaemia produces a sweaty feet odour from isovaleric acid. It results from isovaleryl-CoA dehydrogenase deficiency and is diagnosed by urine organic acid analysis showing isovalerylglycine.
How is acute hyperammonaemia treated in organic acidurias?
Acute treatment stops protein intake, provides glucose and calories, and corrects acidosis. Ammonia scavengers such as sodium benzoate and sodium phenylacetate are added, and dialysis is used in severe or refractory cases.
Why is thiamine tried in maple syrup urine disease?
Thiamine pyrophosphate is the cofactor of the branched chain ketoacid dehydrogenase complex, so a thiamine-responsive variant of maple syrup urine disease exists. A trial of high-dose thiamine is therefore worthwhile in suspected cases.