carnitine palmitoyl transferase II deficiency, myopathic form

Carnitine palmitoyl transferase II deficiency, myopathic form is a metabolic muscle disorder that interferes with the breakdown of long-chain fatty acids inside the mitochondria. It results from genetic changes in the CPT2 gene, which provides instructions for an enzyme needed to move these fats into the energy-producing parts of the cell. The condition usually appears in adolescence or adulthood, affecting people of any sex, and tends to present during periods of prolonged exercise, fasting, fever, or exposure to cold. Precise prevalence is not well established, but it is considered uncommon. Most individuals experience episodic symptoms rather than continuous weakness, and many lead active lives between attacks.

Severity and symptoms vary widely between individuals. Not all affected people experience every feature and the frequency, length, and severity of attacks can differ even within the same family. Musculoskeletal system: The hallmark is exercise-induced or stress-induced muscle pain (myalgia) that may begin during prolonged activity, illness, fasting, or cold exposure. Episodes can lead to muscle weakness, spasms, or cramps and, in some individuals, measurable loss of muscle bulk over time. Renal and urinary system: Muscle breakdown may release myoglobin into the bloodstream, causing dark red-brown urine (myoglobinuria). Repeated severe episodes can strain the kidneys and, in a small subset, lead to acute kidney injury or chronic kidney disease. Metabolic findings: Laboratory tests during crises typically show elevated creatine kinase, long-chain acylcarnitines, and occasionally high levels of long-chain fatty acids. Between episodes these values may return to normal. Less common or variable features: Some individuals report cold-induced cramps, intermittent painful spasms, or elevated lipid stores in muscle cells documented on biopsy.

The disorder is caused by pathogenic variants in the CPT2 gene. The CPT2 enzyme works with carnitine to shuttle long-chain fatty acids into mitochondria, where they are converted into energy. When the enzyme is partially impaired, muscle cells cannot meet energy demands during periods of high need, leading to breakdown of muscle fibers and release of myoglobin. Multiple inheritance patterns have been reported. Most families follow an autosomal recessive pattern, meaning a person must inherit two altered copies of CPT2, one from each parent, to develop symptoms. Carrier parents, who each have a single altered copy, are typically healthy but have a 25 percent chance with each pregnancy of having an affected child. Less commonly, autosomal dominant variants have been identified, where a single altered copy can be sufficient to cause disease; expression in these families can range from asymptomatic to symptomatic (variable expressivity). Even within dominant families, not everyone who carries the variant develops symptoms, suggesting reduced penetrance. Because the condition is uncommon, it may be more frequently observed in families where parents share a common ancestor, which increases the chance they carry the same rare variant. Genetic counseling is recommended for at-risk relatives and for family planning.

Currently, management focuses on supportive measures tailored to each individual. Avoiding known triggers such as prolonged strenuous exercise, fasting, dehydration, or exposure to cold can prevent many episodes. During acute attacks, prompt medical attention with hydration and monitoring of kidney function helps reduce complications. Long-term management includes regular surveillance for potential complications such as kidney impairment and cumulative muscle damage. A multidisciplinary team—typically including neurology, metabolic specialists, nephrology, nutrition, and physical therapy—guides preventive strategies, monitors laboratory values, and coordinates emergency plans for rhabdomyolysis. Because individual triggers and responses differ, ongoing monitoring allows treatment plans to be adjusted over time. Genetic counseling offers additional support for affected individuals and their relatives.

Outcomes vary depending on how often episodes occur, how quickly they are treated, and whether complications such as kidney injury develop. Many people remain symptom-free between attacks and maintain normal strength, especially when they learn to avoid personal triggers. Severe rhabdomyolysis can cause temporary or permanent kidney damage, but this is uncommon with attentive care. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with metabolic specialists familiar with this condition and to seek genetic counseling for individualized guidance.