Essential Blood Work for Restless Legs Syndrome (RLS) Diagnosis
Serum ferritin and transferrin saturation are the most important blood tests for RLS diagnosis and management, with ferritin levels ≤75 ng/mL or transferrin saturation <20% indicating a need for iron supplementation. 1
Primary Laboratory Tests for RLS
Iron Studies:
- Serum ferritin (morning collection recommended)
- Transferrin saturation
- Complete blood count (to assess for anemia)
Timing Considerations:
- Morning testing is preferred
- Patient should avoid iron supplements/iron-containing foods for at least 24 hours before testing 1
Secondary Laboratory Tests Based on Clinical Presentation
When evaluating patients with suspected RLS, additional testing may be warranted to identify secondary causes:
Renal Function:
Metabolic Screening:
- Comprehensive metabolic panel
- Calcium and phosphorus (rare association with hyperparathyroidism) 3
Other Considerations:
- Vitamin B12 and folate levels (to rule out deficiencies that may cause neuropathy)
- HbA1c or fasting glucose (if diabetic neuropathy is suspected) 4
Interpretation of Iron Studies
| Parameter | Threshold | Clinical Implication |
|---|---|---|
| Serum ferritin | ≤75 ng/mL (adults) | Consider oral or IV iron supplementation [1] |
| Serum ferritin | <50 ng/mL (children) | Indication for iron supplementation in pediatric RLS [1] |
| Transferrin saturation | <20% | Consider iron supplementation [1] |
| Serum ferritin | 75-100 ng/mL | Consider IV iron only [1] |
Clinical Context for Laboratory Testing
Laboratory testing for RLS should be performed in the context of clinical diagnosis based on the five essential criteria established by the International Restless Legs Syndrome Study Group (IRLSSG) 5:
- An urge to move the legs usually accompanied by uncomfortable sensations
- Symptoms begin or worsen during periods of rest or inactivity
- Symptoms are partially or totally relieved by movement
- Symptoms worsen in the evening or night
- Symptoms are not solely accounted for by another medical condition
Common Pitfalls in RLS Diagnosis and Testing
- Failure to test iron parameters: Iron deficiency is a major treatable cause of RLS, yet iron studies are often overlooked 6, 2
- Misinterpreting "normal" ferritin: While laboratory "normal" ranges for ferritin may extend to 20-30 ng/mL, RLS patients may benefit from iron supplementation at higher levels (≤75 ng/mL) 1
- Not considering secondary causes: RLS can be secondary to conditions like renal disease, pregnancy, and certain medications 2, 4
- Confusing RLS with mimics: Conditions like leg cramps, venous stasis, positional discomfort, and arthritis can mimic RLS symptoms 5
By conducting appropriate blood work and interpreting results in the context of clinical presentation, clinicians can better diagnose RLS and identify treatable causes, ultimately improving patient outcomes and quality of life.