Very long-chain acyl-CoA dehydrogenase deficiency

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a condition that prevents the body from converting certain fats into energy, particularly during periods without food (fasting).

There are three forms of VLCAD deficiency, and they are defined by when the signs and symptoms of the condition begin. The early-onset form is the most severe and begins in infancy. Signs and symptoms can include lack of energy (lethargy) and muscle weakness. People with VCLAD deficiency can have low blood sugar (glucose), known as hypoglycemia. Affected individuals are also at risk for serious complications such, as liver abnormalities and life-threatening heart problems.

Individuals with childhood-onset VLCAD deficiency typically experience an enlarged liver (hepatomegaly) and low blood glucose. This form is sometimes referred to as the hepatic or hypoketotic hypoglycemic form because of these signs. Additional signs and symptoms include other liver problems or muscle weakness.

The adult-onset form, which begins in adolescence or adulthood, usually involves muscle pain and the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a large amount of a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobinuria causes the urine to be red or brown.

In both children and adults, problems related to VLCAD deficiency can be triggered by periods of fasting, illness, exercise, and exposure to hot or cold temperatures. In children, this disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome occur in children who take aspirin during these viral infections.

ORPHANET DEFINITION Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD) is an inherited disorder of mitochondrial long-chain fatty acid oxidation with a variable presentation including: cardiomyopathy, hypoketotic hypoglycemia, liver disease, exercise intolerance and rhabdomyolysis.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Prevalence at birth: 1-9 / 100 000; Australia; Value and class. Prevalence at birth: 1-9 / 100 000; United States; Value and class. Point prevalence: 1-9 / 100 000; Germany; Value and class. Prevalence at birth: 1-9 / 1 000 000; Czech Republic; Value and class.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Increased circulating free fatty acid level · Frequent (79-30%)

A higher than normal levels of the fatty acids which can occur in plasma as a result of lipolysis in adipose tissue or when plasma triacyglycerols are taken into tissues.

Atrial septal defect · Occasional (29-5%)

Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.

Elevated circulating creatine kinase concentration · Occasional (29-5%)

The activity of creatine kinase in the blood circulation is above the upper limit of normal.

Elevated circulating hepatic transaminase concentration · Occasional (29-5%)

Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.

Episodic tachypnea · Occasional (29-5%)

Episodes of very rapid breathing.

Exercise-induced rhabdomyolysis · Occasional (29-5%)

Rhabdomyolysis induced by exercise.

Feeding difficulties · Occasional (29-5%)

Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.

Hepatomegaly · Occasional (29-5%)

Abnormally increased size of the liver.

Hypoketotic hypoglycemia · Occasional (29-5%)

A decreased concentration of glucose in the blood associated with a reduced concentration of ketone bodies.

Hypothermia · Occasional (29-5%)

Reduced body temperature due to failed thermoregulation.

Jaundice · Occasional (29-5%)

Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.

Overweight · Occasional (29-5%)

Increased body weight with a body mass index of 25-29.9 kg per square meter.

Patent foramen ovale · Occasional (29-5%)

Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria.

Respiratory distress · Occasional (29-5%)

Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.

Other findings in the same source

From: Orphanet

Additional reported features include Small for gestational age (Occasional (29-5%)); Ventricular septal defect (Occasional (29-5%)); Anteriorly placed anus (Very rare (<4-1%)); Arrhythmia (Very rare (<4-1%)); Atrioventricular block (Very rare (<4-1%)); Dilated cardiomyopathy (Very rare (<4-1%)); Enlarged cisterna magna (Very rare (<4-1%)); Floppy infant (Very rare (<4-1%)); Hyperammonemia (Very rare (<4-1%)); Hypocalcemia (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Infancy; Neonatal

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Prevalence at birth: 1-9 / 100 000; Australia; Value and class. Prevalence at birth: 1-9 / 100 000; United States; Value and class. Point prevalence: 1-9 / 100 000; Germany; Value and class. Prevalence at birth: 1-9 / 1 000 000; Czech Republic; Value and class.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Very long-chain acyl-CoA dehydrogenase deficiency is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Very long-chain acyl-CoA dehydrogenase deficiency. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.