Carnitine palmitoyltransferase I deficiency

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Carnitine palmitoyltransferase I (CPT I) deficiency is a condition that prevents the body from using certain fats for energy.

The signs and symptoms of CPT I deficiency are often brought on by episodes of increased energy demands in the body such as illness or periods of fasting. During these times, affected individuals usually develop low levels of glucose in the blood and a low level of ketones, which are normally produced when fats are broken down to be used for energy. Together, these signs are called hypoketotic hypoglycemia. This may cause individuals to experience confusion, seizures, or a lack of energy (lethargy).

People with CPT I deficiency can also develop an enlarged liver (hepatomegaly) that is not able to remove toxins from the blood efficiently. These toxins build up and can affect brain function (hepatic encephalopathy). As long as no brain damage occurs during these episodes of hepatic encephalopathy, individuals with CPT I deficiency often have normal development.

Health can decline quickly in people with CPT I deficiency. Affected individuals are encouraged to avoid prolonged fasting to prevent serious health problems. Individuals with CPT I deficiency are at risk for nervous system damage, liver failure, coma, and sudden death. These problems can begin any time between infancy to adulthood, though some individuals experience no health problems at all.

CPT I deficiency is often detected shortly after birth by newborn screening, which identifies abnormal levels of certain compounds in the blood. People with CPT I deficiency have high levels of a compound called carnitine. 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 caused mutations) in the CPT1A gene cause CPT I deficiency. This gene provides instructions for making an enzyme called carnitine palmitoyltransferase 1A, which is found in the liver.

Carnitine palmitoyltransferase 1A is essential for fatty acid oxidation, which is the multistep process that breaks down (metabolizes) fats and converts them into energy. During periods of fasting, fats are an important energy source for the liver and other tissues. Within liver cells, fatty acid oxidation takes place within mitochondria, which are the energy-producing centers. Before entering mitochondria, a group of fats called long-chain fatty acids must first be attached to carnitine. Carnitine palmitoyltransferase 1A connects carnitine to long-chain fatty acids so they can enter mitochondria and be metabolized to produce energy.

Variants in the CPT1A gene severely reduce or eliminate the activity of carnitine palmitoyltransferase 1A. As a result, there are not enough enzymes available to attach carnitine to long-chain fatty acids when energy demands are high. Without carnitine, these fatty acids cannot enter mitochondria to be broken down and used for energy. Reduced energy production can lead to some of the features of CPT I deficiency, such as hypoketotic hypoglycemia. Fatty acids and related compounds may also build up in cells and damage the liver, heart, and brain. This abnormal buildup causes the other signs and symptoms of CPT I deficiency.

Conditions that disrupt the metabolism of fatty acids, including CPT I deficiency, are known as fatty acid oxidation disorders.

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. However, women who have one CPT1A gene variant and who are pregnant with a fetus who has two CPT1A gene variants are at risk of developing a condition called acute fatty liver of pregnancy (AFLP). AFLP begins with abdominal pain and can rapidly progress to liver failure.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

CPT I deficiency is a rare disorder, though its prevalence varies worldwide. It is estimated to occur in 1 in 750,000 to 2,000,000 infants in the United States. CPT I deficiency is more common in certain populations, including some Native Alaskan populations and some Native Pacific Island populations. In certain regions of China, CPT I deficiency is estimated to have an incidence of 1 in 102,388 infants.

Which doctor should you see?

The suggested department for discussing Carnitine palmitoyltransferase I deficiency is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with 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.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Carnitine palmitoyltransferase I 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.