What is very long-chain acyl-CoA dehydrogenase deficiency?

Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a metabolic disorder caused by impaired fatty acid metabolism, belonging to autosomal recessive inherited diseases.

Which department should be consulted for VLCADD?

English name: very long-chain acyl-CoA dehydrogenase deficiency, VLCADD.

Aliases: Very long-chain acyl-CoA dehydrogenase deficiency, Acyl-CoA dehydrogenase deficiency, Ultra-long-chain acyl-CoA dehydrogenase deficiency.

Departments to visit: Pediatrics, Neonatology.

What causes VLCADD?

It results from gene mutations in the very long-chain acyl-CoA dehydrogenase, leading to impaired fatty acid metabolism. This enzyme is crucial for mitochondrial fatty acid β-oxidation.

Who is commonly affected by VLCADD?

Different types occur in distinct populations: newborns and early infancy (most common), late infancy and childhood, or adolescence and adulthood.

What are the symptoms of VLCADD?

Clinical manifestations vary in severity and onset age, ranging from asymptomatic cases to fatal outcomes. Three main types exist:

1. Cardiomyopathic type:

• Primarily occurs in newborns and early infancy, representing the most severe form with cardiac and multi-organ failure.
• High mortality rate due to critical conditions like hypoglycemia, Reye-like syndrome, sudden neonatal death, hypertrophic/dilated cardiomyopathy, arrhythmias, hepatomegaly, and elevated creatine kinase.

2. Hepatic type:

• Manifests in late infancy/childhood with milder symptoms: hepatomegaly, fasting intolerance, and hypoketotic hypoglycemia without cardiac involvement.
• Untreated cases may still be life-threatening.

3. Myopathic type:

• Occurs in adolescents/adults with milder symptoms: rhabdomyolysis, myoglobinuria (triggered by exercise/infection/fasting), muscle pain, or weakness. No cardiac or hypoglycemic issues typically.

How is VLCADD diagnosed?

Diagnosis relies on clinical presentation, biochemical tests, and genetic analysis:

1. Suspicion based on symptoms.
2. Newborn screening (NBS): Abnormal results warrant blood acylcarnitine profiling and ACADVL gene testing.
3. Elevated C14:1 (>1 mmol/L) in acylcarnitine analysis strongly suggests VLCADD; confirmed by two pathogenic ACADVL mutations.
4. Special tests (e.g., fibroblast β-oxidation assay, enzyme activity analysis) for cases with one mutation.
5. Fatty acid oxidation flux analysis (e.g., LC-FAO) may predict symptom onset.

How is VLCADD treated?

No cure exists. Management focuses on preventing fasting/stress, maintaining a high-carbohydrate/low-fat diet with medium-chain triglycerides (MCT), and symptom control.

1. Feeding schedule:

• Newborns: Feed every 3 hours; infants <6 months: every 4 hours; older infants/children/adults gradually extend intervals.
• Cornstarch at night/activity to sustain glucose and reduce fat breakdown.

2. Dietary control:

High-carb, low-fat (especially long-chain fats) with adequate protein. Symptomatic infants stop breastfeeding (high fat content).

• Cardiomyopathic type: 90% fat intake as MCT; specialized formulas for infants; older children limit long-chain fats to 10% calories.
• Hepatic/myopathic types: 50% MCT in fats; "heart-healthy" diet post-infancy.

What is the prognosis for VLCADD?

Prognosis depends on onset age and dietary compliance. Early-onset (especially cardiomyopathy) has higher mortality. Lifelong timed meals and balanced nutrition are crucial.

How to prevent VLCADD?

• Preconception genetic counseling and prenatal testing.
• Early diagnosis and proper feeding to prevent complications.
• Carry emergency glucose sources (e.g., candy).
• Psychological support for patients/families.