Conditions · Metabolism: amino acids and the urea cycle
Propionic acidaemia !
In propionic acidaemia propionyl-CoA is not processed; acids build up and cause acidosis crises, high ammonia and damage to heart and brain.
Updated 2026-11-01
Structures involved
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In biochemistry
- Propionyl-CoA to succinyl-CoA: Step 1 · Propionyl-CoA carboxylase (PCC)
- Carbamoyl phosphate synthetase I (CPS-I)
- Branched-chain α-keto acid dehydrogenase (BCKDH)
- Glucogenic and ketogenic amino acids
What it is
An inherited organic acidaemia from lack of propionyl-CoA carboxylase, a biotin-dependent enzyme.
Who gets it
It affects about 1 in 100,000 people in the United States; it is more common in Saudi Arabia, some Amish communities and the Inuit of Greenland.
Causes
- Variants of PCCA or PCCB (autosomal recessive)
Risk factors
- Carrier parents
- Consanguinity
- Infections and fasting (crises)
Pathophysiology
Propionyl-CoA carboxylase turns propionyl-CoA into methylmalonyl-CoA. Without it, propionyl-CoA, propionic acid, 3-hydroxypropionate and methylcitrate build up. There is high anion gap acidosis, hyperammonaemia (less N-acetylglutamate), bone marrow suppression and damage to basal ganglia and myocardium.
Symptoms and signs
- Poor feeding, vomiting and lethargy in the first days
- Hypotonia and seizures
- Low neutrophils and platelets
- Developmental delay
- Later: cardiomyopathy and arrhythmias
Diagnosis
- Clinical
- Neonatal encephalopathy with acidosis; expanded newborn screening with high propionylcarnitine.
- Tests
- High propionylcarnitine (C3); urinary 3-hydroxypropionate, methylcitrate and propionylglycine, without high methylmalonic acid; ammonia, gases and blood count; genetic testing.
- Imaging
- Echocardiography for cardiomyopathy; brain MRI for basal ganglia lesions.
Treatment
- Acute
- In a crisis: stop protein, give glucose and lipids, correct acidosis, carglumic acid or scavengers for ammonia, and dialysis if severe
- Lifestyle
- Low-protein diet with a formula free of valine, isoleucine, methionine and threonine
- Medical
- Carnitine and metronidazole to cut propionate made by gut bacteria
- Surgical
- Liver transplant in selected cases
- Follow-up
- Cardiology follow-up with echocardiography and electrocardiography
Complications
- Cardiomyopathy and long QT
- Pancreatitis
- Basal ganglia lesions
- Intellectual disability
- Infections from neutropenia
Prognosis
Neonatal forms carry a high risk of death and sequelae; early diagnosis and dietary control improve survival.
Test yourself
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Which vitamin does propionyl-CoA carboxylase need?
Biotin (B7), like all carboxylases that fix CO₂.
What separates propionic from methylmalonic acidaemia in urine?
In propionic acidaemia methylmalonic acid does not rise; methylcitrate and 3-hydroxypropionate do appear.
Which heart complication is typical?
Cardiomyopathy, sometimes with long QT and arrhythmias, even with good metabolic control.
Related conditions
- Methylmalonic acidaemia
- Hyperammonaemia
- Maple syrup urine disease
- Chronic kidney disease
- Acute pancreatitis
- Heart failure
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Propionic acidemia: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); PCCA gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Propionyl-CoA catabolism (Reactome, 2026).
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