Carnitine palmitoyltransferase 2 deficiency

Alternate names

Carnitine palmitoyltransferase deficiency type 2; CPT2; Carnitine palmitoyltransferase II (CPT II) deficiency

Definition

Carnitine palmitoyltransferase 2 (CPT2) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting).

Epidemiology

• CPT II deficiency is a rare syndrome.
• The lethal neonatal form has been described in at least 18 families, while the severe infantile hepatocardiomuscular form has been identified in 30 families.
• The myopathic form occurs most frequently, with more than 300 reported cases.

Cause

• Mutations in the CPT2 gene cause CPT2 deficiency.
• This gene provides instructions for making an enzyme called carnitine palmitoyltransferase 2.
• This enzyme is essential for fatty acid oxidation, which is the multistep process that breaks down (metabolizes) fats and converts them into energy.

Gene mutations

• Mutations in the CPT2 gene reduce the activity of carnitine palmitoyltransferase 2.
• Without enough of this enzyme, carnitine is not removed from long-chain fatty acids.
• As a result, these fatty acids cannot be metabolized to produce energy.
• Reduced energy production can lead to some of the features of CPT II deficiency, such as hypoketotic hypoglycemia, myalgia, and weakness.

Inheritance

Autosomal recessive inheritance, a 25% chance

It is inherited in an autosomal recessive pattern.

Types and symptoms

• There are three main types of CPT2 deficiency: a lethal neonatal form, a severe infantile hepatocardiomuscular form, and a myopathic form.
• The neonatal and infantile forms are severe multisystemic diseases characterized by liver failure with hypoketotic hypoglycemia (extremely low levels of ketones (substances produced when fat cells break down in the blood) and low blood sugar), cardiomyopathy, seizures, and early death.
• The myopathic form is characterized by exercise-induced muscle pain and weakness and occasional myoglobinuria (rust-colored urine indicating breakdown of muscle tissue).

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Muscle weakness(Muscular weakness)
• Reduced carnitine O-palmitoyltransferase level

30%-79% of people have these symptoms

• Decreased plasma free carnitine
• Decreased plasma total carnitine
• Elevated plasma acylcarnitine levels
• Elevated serum creatine kinase(Elevated blood creatine phosphokinase)
• Exercise intolerance(Decreased ability to exercise)
• Exercise-induced myalgia(Exercise-induced muscle pain)
• Hyperlipidemia(Elevated lipids in blood)
• Myoglobinuria
• Myopathy(Muscle tissue disease)
• Red-brown urine

5%-29% of people have these symptoms

• Cold-induced muscle cramps
• Episodic abdominal pain
• Exercise-induced muscle cramps(Exercise-induced muscle cramping)
• Headache(Headaches)
• Hepatomegaly(Enlarged liver)
• Intermittent painful muscle spasms
• Renal tubular epithelial necrosis
• Rhabdomyolysis(Breakdown of skeletal muscle)
• Seizure
• Stage 5 chronic kidney disease
• Tubulointerstitial nephritis

1%-4% of people have these symptoms

• Abnormality of the basal ganglia
• Agenesis of corpus callosum
• Arrhythmia(Abnormal heart rate)
• Cardiomyopathy(Disease of the heart muscle)
• Cerebellar vermis hypoplasia
• Cerebral calcification(Abnormal deposits of calcium in the brain)
• Coma
• Cystic renal dysplasia
• Hepatic calcification
• Hepatic failure(Liver failure)
• Hydrocephalus(Too much cerebrospinal fluid in the brain)
• Hypoketotic hypoglycemia
• Neonatal respiratory distress(Infantile respiratory distress)
• Pachygyria(Fewer and broader ridges in brain)
• Polycystic kidney dysplasia
• Polymicrogyria(More grooves in brain)

Diagnosis

The diagnosis of CPT II deficiency is established in a proband by the finding of reduced CPT enzyme activity in muscle or the identification of biallelic pathogenic variants in CPT2 on molecular genetic testing.<ref>Wieser T. Carnitine Palmitoyltransferase II Deficiency. 2004 Aug 27 [Updated 2019 Jan 3]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1253/</ref>[1].

Treatment

• High-carbohydrate (70%) and low-fat (<20%) diet to provide fuel for glycolysis
• Use of carnitine to convert potentially toxic long-chain acyl-CoAs to acylcarnitines
• Avoidance of known triggers.<ref>Wieser T. Carnitine Palmitoyltransferase II Deficiency. 2004 Aug 27 [Updated 2019 Jan 3]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1253/</ref>[2].

References

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NIH genetic and rare disease info

• NIH info on Carnitine palmitoyltransferase 2 deficiency

Carnitine palmitoyltransferase 2 deficiency is a rare disease.

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