Can low serum ferritin contribute to facial motor tics and restless‑leg syndrome, and what is the recommended evaluation and treatment approach?

Facial Tics and Restless Leg Syndrome: Iron Deficiency Connection

Low serum ferritin can contribute to restless leg syndrome but is not established as a cause of facial motor tics; evaluate and treat iron deficiency in RLS using specific ferritin thresholds (≤75 ng/mL in adults, <50 ng/mL in children), while facial tics require separate neurological evaluation.

Iron Deficiency and Restless Leg Syndrome

The American Academy of Sleep Medicine recommends checking morning fasting serum ferritin and transferrin saturation in all patients with clinically significant RLS, ideally after avoiding iron-containing supplements for at least 24 hours. 1

RLS-Specific Iron Thresholds (Different from General Population)

• Adults with RLS: Supplement iron if ferritin ≤75 ng/mL or transferrin saturation <20% 1, 2
• Children with RLS: Supplement iron if ferritin <50 ng/mL 1, 3
• These thresholds are substantially higher than standard anemia cutoffs because brain iron deficiency plays a key role in RLS pathophysiology even when serum iron appears normal 2

Evidence Linking Low Ferritin to RLS

• Low serum ferritin is significantly associated with RLS augmentation (paradoxical worsening on dopaminergic therapy), with augmented patients having mean ferritin of 55.8 µg/L versus 100.6 µg/L in non-augmented patients 4, 5
• A randomized, double-blind, placebo-controlled trial demonstrated that oral iron therapy in RLS patients with low-normal ferritin (mean 40.6 ng/mL) produced statistically significant improvement in International RLS Scale scores (decrease of 10.3 points versus 1.14 in placebo, p=0.01) 6
• Approximately one-third of RLS patients have ferritin levels <50 µg/L, and there is an inverse correlation between RLS severity and ferritin levels 5

Iron Deficiency and Facial Tics: Lack of Established Connection

There is no evidence in current guidelines or high-quality research linking low ferritin specifically to facial motor tics. The provided evidence focuses exclusively on RLS and does not address tic disorders. Facial tics typically require evaluation for:

• Primary tic disorders (Tourette syndrome, chronic motor tic disorder)
• Medication-induced movement disorders
• Neurological conditions affecting the basal ganglia
• Psychogenic movement disorders

Evaluation Approach

Step 1: Obtain Iron Studies

• Draw morning fasting ferritin and transferrin saturation after 24-hour iron-free interval 1, 3
• Include complete blood count to assess for anemia 7
• Measure transferrin saturation to rule out hemochromatosis before initiating iron therapy (transferrin saturation >45% warrants further evaluation) 7

Step 2: Address Exacerbating Factors for RLS

• Eliminate alcohol, caffeine, antihistaminergic medications, serotonergic medications, and antidopaminergic medications 1, 8
• Evaluate and treat obstructive sleep apnea if present 1, 8

Step 3: Initiate Iron Supplementation (If Indicated)

For ferritin ≤75 ng/mL or transferrin saturation <20%:

• Oral iron: Ferrous sulfate 325 mg daily or every other day (conditional recommendation, moderate certainty) 2, 8
• IV iron: Ferric carboxymaltose 750-1000 mg in one or two infusions (strong recommendation, moderate certainty) if oral iron fails, is not tolerated, or ferritin is 75-100 ng/mL 1, 2, 8
• Continue oral iron for 3-6 months after symptom resolution to replenish stores 2
• Monitor ferritin every 6-12 months indefinitely, as RLS symptoms may recur if iron stores decline 2, 3

Step 4: First-Line Pharmacologic Treatment for RLS (If Iron Alone Insufficient)

The American Academy of Sleep Medicine strongly recommends alpha-2-delta ligands as first-line therapy for RLS (strong recommendation, moderate certainty of evidence): 1, 2, 3, 8

• Gabapentin enacarbil (strong recommendation) 1, 8
• Gabapentin: Start 300 mg three times daily, titrate by 300 mg/day every 3-7 days to maintenance dose of 1800-2400 mg/day divided TID (strong recommendation) 1, 3, 8
• Pregabalin: Start 75 mg once daily 1-2 hours before bedtime, titrate to 150-300 mg daily as needed (strong recommendation) 2, 3, 8

Step 5: Avoid Dopamine Agonists as First-Line Therapy

• The American Academy of Sleep Medicine suggests against standard use of dopamine agonists (pramipexole, ropinirole, rotigotine) due to 7-10% annual augmentation risk (conditional recommendation, moderate certainty) 1, 3, 8
• Augmentation manifests as earlier daily symptom onset, increased intensity, and spread to arms or trunk 3, 4, 5
• Low ferritin levels are associated with higher augmentation risk, making iron repletion even more critical before considering dopaminergic agents 4, 5

Treatment Algorithm Summary

1. Check morning fasting ferritin and transferrin saturation after 24-hour iron-free interval 1, 3
2. If ferritin ≤75 ng/mL or transferrin saturation <20%: Start oral ferrous sulfate 325 mg daily/every other day 2, 8
3. Eliminate RLS exacerbating factors (alcohol, caffeine, antihistamines, serotonergics, antidopaminergics) 1, 8
4. Reassess in 3 months: If symptoms persist despite iron repletion, initiate alpha-2-delta ligand (gabapentin, gabapentin enacarbil, or pregabalin) 2, 3, 8
5. Consider IV ferric carboxymaltose if oral iron fails or ferritin remains 75-100 ng/mL 1, 2
6. Monitor ferritin every 6-12 months indefinitely to prevent recurrence 2, 3

Critical Pitfalls to Avoid

• Do not assume facial tics are related to iron deficiency—they require separate neurological evaluation and are not addressed in RLS guidelines [1-9]
• Do not use general population ferritin thresholds for RLS—the RLS-specific threshold is ≤75 ng/mL, substantially higher than anemia cutoffs 1, 2
• Do not start dopamine agonists as first-line therapy—alpha-2-delta ligands are now strongly recommended due to lower augmentation risk 1, 3, 8
• Do not initiate iron therapy without checking transferrin saturation—elevated levels (>45%) may indicate hemochromatosis and require further evaluation before iron supplementation 7
• Do not discontinue iron supplementation after symptom resolution—continue for 3-6 months to replenish stores and monitor every 6-12 months indefinitely 2, 3