What laboratory tests are recommended for diagnosing Restless Legs Syndrome (RLS)?

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From the Guidelines

For patients with restless legs syndrome (RLS), clinicians should regularly check serum iron studies, including ferritin and transferrin saturation, as the primary laboratory tests. These tests are crucial in determining the need for iron supplementation, which can significantly impact the management of RLS symptoms 1. According to the American Academy of Sleep Medicine clinical practice guideline, testing should ideally be administered in the morning, avoiding all iron-containing supplements and foods at least 24 hours prior to blood draw 1.

Key Laboratory Tests

  • Serum ferritin
  • Transferrin saturation (calculated from iron and total iron binding capacity) These tests help identify iron deficiency, which is strongly associated with RLS symptoms, and guide the decision to use oral or intravenous (IV) iron treatment 1.

Additional Considerations

  • Complete blood count (CBC) and renal function tests (BUN, creatinine) may also be valuable in identifying underlying causes of RLS symptoms
  • Vitamin B12 and folate levels, as well as thyroid function tests, can help rule out other conditions that may mimic or exacerbate RLS symptoms However, the primary focus should be on serum iron studies, as iron deficiency is a key factor in RLS management 1.

From the Research

Laboratory Tests for Restless Legs Syndrome

To diagnose and manage restless legs syndrome (RLS), several laboratory tests can be useful. The following are some of the key tests:

  • Iron measures, including:
    • Ferritin levels 2, 3, 4
    • Transferrin saturation 2, 3
  • These tests can help identify iron deficiency, which is a common cause of RLS 2, 3, 4
  • Other tests that may be useful in certain cases include:
    • Bone marrow examination to diagnose iron deficiency 4
    • Genetic testing to identify genetic predisposition 2, 5
    • Tests to rule out other conditions that may be contributing to RLS, such as kidney disease or diabetes 5

Interpretation of Laboratory Results

When interpreting laboratory results, it's essential to consider the following:

  • Ferritin levels can be elevated in cases of inflammation, which may mask iron deficiency 4
  • Transferrin saturation can be useful in diagnosing iron overload, such as in hemochromatosis 3
  • A thorough medical history and physical examination are also crucial in diagnosing and managing RLS 2, 5, 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Restless Legs Syndrome: Contemporary Diagnosis and Treatment.

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2021

Research

Restless legs syndrome.

Nature reviews. Disease primers, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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