carnitine palmitoyltransferase II deficiency

What is Carnitine Palmitoyltransferase II Deficiency?

Carnitine palmitoyltransferase II (CPT II) deficiency is a rare genetic disorder that affects the body's ability to convert certain fats into energy. This condition is characterized by an enzymatic defect in the CPT2 gene, which prevents long-chain fatty acids from being transported into the mitochondria for utilization as an energy source.

Types of CPT II Deficiency

There are three main types of CPT II deficiency, each with varying degrees of severity:

• Lethal Neonatal Form: This is the most severe form, characterized by liver failure and hypoketotic hypoglycemia in newborns.
• Severe Infantile Hepatocardiomuscular Form: This form presents with severe multisystemic disease, including liver failure, heart problems, and muscle weakness, typically in infancy.
• Myopathic Form: This is the least severe form, manifesting as muscle weakness and other symptoms, often appearing from infancy to adulthood.

Symptoms and Clinical Features

The myopathic form of CPT II deficiency is characterized by:

• Muscle weakness
• Fatigue
• Myalgia (muscle pain)
• Myoglobinuria (presence of myoglobin in the urine)

These symptoms can vary in severity and may be triggered by fasting or other periods without food.

Prevalence and Genetics

CPT II deficiency is an autosomal recessively inherited condition, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disorder. The prevalence of this condition is extremely rare, with only a few reported cases worldwide.

References:

• [1] CPT II deficiency is characterized by an enzymatic defect in the CPT2 gene, preventing long-chain fatty acids from being transported into the mitochondria for utilization as an energy source. (Source: #3)
• There are three main types of CPT II deficiency, each with varying degrees of severity. (Source: #7)
• The myopathic form is characterized by muscle weakness, fatigue, myalgia, and myoglobinuria. (Source: #6)

Carnitine palmitoyltransferase II (CPT II) deficiency is a rare genetic disorder that affects the body's ability to convert fatty acids into energy. The signs and symptoms of CPT II deficiency can vary in severity and may include:

• Recurring episodes of hypoketotic hypoglycemia: This refers to low blood sugar levels due to an inability to properly metabolize fatty acids [1].
• Seizures: Seizures are a common symptom of CPT II deficiency, particularly in the severe forms of the disease [3][6].
• Enlarged liver (hepatomegaly): The liver may become enlarged due to the accumulation of toxic substances [1][6].
• Cardiomyopathy: This refers to a weakening of the heart muscle, which can lead to irregular heartbeat and other cardiac problems [2][5].
• Irregular heartbeat (arrhythmia): Abnormal heart rhythms are a common symptom of CPT II deficiency [3].
• Liver failure: In severe cases, liver failure may occur due to the accumulation of toxic substances [4][5].
• Abnormalities associated with the brain and kidneys: These organs may be affected in some individuals with CPT II deficiency [3].
• Low muscle tone (hypotonia): Weakness or low muscle tone is a common early sign of CPT II deficiency, particularly in infants [9].

It's worth noting that the severity and presentation of CPT II deficiency can vary widely among individuals, even within the same family. Some people may experience only mild symptoms, while others may have more severe forms of the disease.

References: [1] Context result 1 [2] Context result 2 [3] Context result 3 [4] Context result 4 [5] Context result 5 [6] Context result 6 [7] Context result 7 [8] Context result 8 [9] Context result 9

Diagnosing Carnitine Palmitoyltransferase II (CPT2) Deficiency

Carnitine palmitoyltransferase II (CPT2) deficiency is a genetic disorder that affects the body's ability to use certain fats for energy. Diagnosing this condition involves several tests and evaluations.

Newborn Screening Tests

Infants with CPT2 deficiency may be diagnosed through standard newborn screening tests [1]. These tests are typically conducted within 24-48 hours of birth.

Medical History and Physical Exam

The process to diagnose CPT2 deficiency starts with a medical history and a physical exam. This is followed by further testing to confirm the diagnosis [1].

Special Blood Tests

Your doctor may conduct special blood tests, such as tandem mass spectrometry of serum/plasma acylcarnitines or tests to measure enzymatic activity, to diagnose CPT2 deficiency [5]. These tests can help identify high amounts of certain fatty acids in the blood.

Signs and Symptoms

The first signs of CPT2 deficiency include brownish red urine (myoglobinuria) and muscle weakness or pain after prolonged exercise or other physical activities [3].

Diagnostic Testing Approaches

Several diagnostic testing approaches are available for CPT2 deficiency, including:

• DNA mutation analysis
• Quantitative analysis of acylcarnitines in blood
• Exome-based NextGen sequencing with CNV analysis (this is the favored testing approach) [8]
• Special enzyme tests

Testing Family Members

Brothers and sisters of an affected child can be tested for CPT2 deficiency using either a DNA test or a special enzyme test [9].

References:

[1] Context 1 [3] Context 3 [5] Context 5 [8] Context 8 [9] Context 9

Treatment Options for Carnitine Palmitoyltransferase II Deficiency

Carnitine palmitoyltransferase II (CPTII) deficiency is a genetic disorder that affects the body's ability to convert fatty acids into energy. While there is no cure for this condition, various treatment options can help manage its symptoms and prevent complications.

• Dietary Adjustments: A low-fat and high-carbohydrate diet combined with exercise restriction can help prevent muscle pain and rhabdomyolysis (a serious condition where muscle tissue breaks down) [1][2].
• Triheptanoin Supplements: Triheptanoin, anaplerotic supplements, have been recommended as a treatment option for CPTII deficiency. In one study, no adverse effects were reported when triheptanoin was used at 30% to 35% of total daily caloric intake [3].
• L-Carnitine Supplementation: L-carnitine supplementation is not typically recommended as a treatment for CPTII deficiency, as it may not be effective in addressing the underlying enzyme deficiency [4].

Important Considerations

While these treatment options can help manage symptoms and prevent complications, it's essential to note that there is no approved drug specifically designed to treat CPTII deficiency. Complete body rest and carbohydrate supplements seem to diminish symptoms, but more research is needed to fully understand their effectiveness [5].

The differential diagnosis for carnitine palmitoyltransferase II (CPT II) deficiency involves considering other conditions that may present with similar symptoms.

• McArdle disease, also known as glycogen storage disease type V, is a genetic disorder that affects the breakdown of glycogen to glucose in muscles. It can cause muscle weakness and fatigue, particularly after exercise [1][2].
• Duchenne muscular dystrophy (DMD) is a genetic disorder that causes progressive muscle degeneration and weakness. It primarily affects boys and can lead to respiratory and cardiac complications [3][4].
• Cytochrome c oxidase deficiency is a rare genetic disorder that affects the production of energy in cells, leading to symptoms such as muscle weakness, seizures, and developmental delays [5][6].
• Complex II deficiency refers to a defect in the electron transport chain, which can lead to symptoms such as muscle weakness, fatigue, and neurological problems [7].

These conditions should be considered in the differential diagnosis of CPT II deficiency, particularly when evaluating patients with similar clinical presentations.