Isobutyryl-CoA dehydrogenase deficiency

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Isobutyryl-CoA dehydrogenase (IBD) deficiency is a condition that disrupts the breakdown of certain proteins. Normally, proteins from food are broken down into amino acids. Amino acids can be further processed to provide energy for growth and development. People with IBD deficiency have problems breaking down the amino acid valine.

Most people with IBD deficiency are asymptomatic, which means that they do not have any signs or symptoms of the condition. If signs or symptoms do appear, they typically show early in life and only last for a short period of time. These signs and symptoms can include weak muscle tone (hypotonia), developmental delays, slow growth, a low number of red blood cells (anemia), and seizures. Because IBD deficiency is rare and often does not cause signs and symptoms, it is difficult to know if the health problems seen in affected individuals are caused by this condition or if those health problems are unrelated to the condition. It is also unclear whether IBD deficiency causes health problems later in life.

Newborn screening, which identifies abnormal levels of certain compounds in the blood, can detect IBD deficiency. People with IBD deficiency have high levels of a compound called carnitine (specifically a form called C4-acylcarnitine). Cells use carnitine, a natural substance that is acquired mostly through the diet, to process fats and produce energy.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in the ACAD8 gene cause IBD deficiency. This gene provides instructions for making the IBD enzyme. This enzyme is found in mitochondria, which are the energy producing centers inside cells. Within mitochondria, the IBD enzyme is involved in breaking down valine. Specifically, this enzyme functions in the third step of this process, which converts the molecule isobutyryl-CoA to the molecule methacrylyl-CoA. This is a critical step in the process of converting the energy from food into a form that cells can use.

ACAD8 gene variants reduce or eliminate the activity of the IBD enzyme. As a result, valine cannot be broken down properly. This may lead to reduced energy production and cause the features of IBD deficiency in some people.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

IBD deficiency is a rare disorder. Worldwide, the prevalence of this disorder is estimated to vary from 1 in 52,000 to 292,000 people.

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.

Decreased circulating carnitine concentration · Frequent (79-30%)

The concentration of carnitine in the blood circulation is below the lower limit of normal.

Dicarboxylic aciduria · Frequent (79-30%)

An increased concentration of dicarboxylic acid in the urine.

Elevated plasma acylcarnitine levels · Frequent (79-30%)

The concentration of fatty acylcarnitine in the blood circulation is above the upper limit of normal.

Delayed speech and language development · Occasional (29-5%)

A degree of language development that is significantly below the norm for a child of a specified age.

Dilated cardiomyopathy · Occasional (29-5%)

Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension, valve disease) or coronary artery disease sufficient to cause global systolic impairment. Right ventricular dilation and dysfunction may be present but are not necessary for the diagnosis.

Hypotonia · Occasional (29-5%)

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

Ketotic hypoglycemia · Occasional (29-5%)

Low blood glucose is accompanied by elevated levels of ketone bodies in the body.

Mild global developmental delay · Occasional (29-5%)

A mild delay in the achievement of motor or mental milestones in the domains of development of a child.

Pulmonic stenosis · Occasional (29-5%)

A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis).

Vomiting · Occasional (29-5%)

Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.

Dehydration · Occasional (29-5%)

Which doctor should you see?

The suggested department for discussing Isobutyryl-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 Isobutyryl-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.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

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.