Is creatine kinase (CK) elevated in Huntington's chorea?

Creatine Kinase Elevation in Huntington's Chorea

Creatine kinase (CK) is not typically elevated in Huntington's chorea, as this neurodegenerative disorder primarily affects the central nervous system rather than causing direct muscle damage.

Pathophysiology and CK in Huntington's Disease

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by:

• Progressive behavioral symptoms
• Choreoathetosis and/or rigidity
• Cognitive dysfunction
• Caused by abnormally increased CAG repeats in the huntingtin gene on chromosome 4 1

Unlike conditions that primarily affect muscle tissue, Huntington's disease primarily causes neurodegeneration, particularly affecting:

• GABAergic medium spiny neurons
• Striatum and cortex 1

The choreiform movements in HD result from basal ganglia dysfunction rather than primary muscle damage. This explains why CK levels, which typically rise with muscle cell damage, are not characteristically elevated in HD patients.

Diagnostic Considerations

When evaluating a patient with suspected Huntington's disease:

• Genetic testing is the diagnostic test of choice, determining CAG repeat number for each allele 1
• Brain MRI without contrast is the optimal imaging modality, though it may be normal early in disease 1
• CK elevation is not a diagnostic feature of HD, unlike in conditions with primary muscle involvement

Contrasting with Other Conditions Where CK is Elevated

CK elevation is more commonly associated with:

1. Primary muscle disorders:

   • Muscular dystrophies (e.g., limb-girdle muscular dystrophy)
   • Inflammatory myopathies
   • Pompe disease (glycogen storage disease type II) 1

2. Immune-related myositis:

   • CK and aldolase are elevated in immune checkpoint inhibitor-related myositis 1

3. Exercise-induced muscle damage:

   • CK levels increase after unaccustomed exercises, especially those including eccentric contractions 1

Research Evidence on CK in HD

Research studies have not demonstrated consistent CK elevation in Huntington's chorea:

• Studies focusing on motor impairment in HD have assessed choreatic movements using various methods but have not identified CK elevation as a characteristic feature 2, 3

• In contrast, chorea-acanthocytosis (a different choreiform disorder) has been associated with elevated serum CK levels and primary skeletal muscle involvement 4

Clinical Implications

When evaluating a patient with choreiform movements:

• Elevated CK would suggest consideration of alternative or additional diagnoses beyond HD
• Normal CK levels would be consistent with HD but are not diagnostic
• The definitive diagnosis of HD relies on genetic testing for CAG repeats in the huntingtin gene

Common Pitfalls to Avoid

• Don't assume that all movement disorders involve muscle damage; many, like HD, are primarily neurological
• Don't rely on CK as a biomarker for HD diagnosis or monitoring
• Don't confuse HD with other choreiform disorders that may have elevated CK, such as chorea-acanthocytosis

In summary, while CK elevation can be a useful biomarker in many neuromuscular conditions, it is not a characteristic feature of Huntington's chorea, which primarily affects the central nervous system rather than causing direct muscle damage.