The symptoms of isovaleric acidaemia vary widely depending on the form and severity. Some people show life-threatening signs within days of birth, while others stay symptom-free for months or years. Stress, illness, or diet may trigger a metabolic crisis. Early recognition of symptoms is crucial to avoid serious brain damage, coma, or death.
This section covers the full range of symptoms—from subtle signs to severe acute episodes. Isovaleric acidaemia presents mainly in two forms: the acute neonatal type and the chronic intermittent type. Each form has distinct symptoms, but some signs overlap.
1. Symptoms in the Acute Neonatal Form
The acute neonatal form usually appears between 3 and 14 days after birth. Babies often seem healthy at first but worsen quickly when they start feeding and processing protein. Without fast treatment, they risk coma and death.
Common signs include:
- Poor feeding: Difficulty suckling or refusal to feed
- Vomiting: Frequent and severe
- Lethargy: Excessive sleepiness or difficulty waking
- Hypotonia: Low muscle tone, floppy limbs
- Seizures: Due to toxin buildup
- Coma: Severe cases may lose consciousness rapidly
- Sweaty feet odour: A distinctive smell caused by isovaleric acid
- Dehydration and acidotic breathing: Rapid breathing to correct blood acidity
- Hypoglycaemia and hyperammonaemia: Low blood sugar and high ammonia levels
If untreated, this form can be fatal. Survivors may face intellectual or developmental delays depending on how long and severe the crisis was.
2. Symptoms in the Chronic Intermittent Form
This form appears later, often in infancy or childhood. Individuals may seem healthy between episodes but fall ill when stressed by infection, fasting, or high protein intake.
Common symptoms include:
- Episodes of vomiting and lethargy: Triggered by illness or protein
- Failure to thrive: Slow growth or poor weight gain
- Developmental delays: Mild to moderate speech or motor delays in some
- Recurrent metabolic crises: Occasional hospitalisations
- Behavioural changes: Irritability or confusion during crises
- Sweaty feet odour: Occasional, more during episodes
- Muscle weakness and fatigue: General tiredness
This form is often mistaken for gastrointestinal illness or behavioural problems until proper testing is done.
3. Subtle and Non-Specific Symptoms
Milder cases, especially those diagnosed early through screening and on treatment, may have subtle symptoms:
- Mild stomach issues like nausea or gas
- Low-grade fatigue, especially during stress or growth
- Trouble tolerating protein-rich foods
- Difficulty concentrating or mild cognitive fatigue
These signs may not cause immediate alarm but show underlying metabolic imbalance. Regular follow-up and blood tests remain important.
4. Symptoms During Metabolic Crises
A metabolic crisis is life-threatening and requires urgent hospital care. Symptoms develop quickly and include:
- Severe vomiting and diarrhoea
- Sudden unconsciousness or coma
- Rapid breathing
- Seizures or convulsions
- High fever or infection signs
- Shock or organ failure signs
Emergency treatment with glucose, fluids, acidosis correction, and metabolite reduction is critical. Families learn to spot early warning signs and seek immediate care.
5. Differences in Presentation Between Age Groups
Newborns face the highest risk due to immature metabolism and immunity. Older children usually have episodic symptoms, which can be confused with common illnesses. Adults with late diagnosis may experience chronic fatigue, brain fog, or protein intolerance.
Conclusion
Symptoms of isovaleric acidaemia range from severe neonatal crises to mild, chronic issues in older individuals. Early signs like vomiting, lethargy, seizures, and poor feeding need urgent attention in newborns. In children, failure to thrive and behavioural changes may signal chronic intermittent disease.
Awareness of these symptoms helps ensure prompt diagnosis and treatment. Newborn screening and clinical vigilance save lives and improve long-term outcomes.
