What labs (CBC (complete blood count), CMP (comprehensive metabolic panel), TSH (thyroid‑stimulating hormone), vitamin B12 and folate, iron studies, and ceruloplasmin and copper if indicated) should be ordered for a newly diagnosed adult with Parkinson’s disease to rule out mimicking conditions?

Laboratory Testing for Parkinson's Disease

For a newly diagnosed adult with Parkinson's disease, order a focused laboratory panel including CBC, comprehensive metabolic panel, TSH, vitamin B12 with metabolites (methylmalonic acid and homocysteine), and ceruloplasmin with serum copper to exclude mimicking conditions—not to diagnose PD itself, which remains a clinical diagnosis. 1

Core Laboratory Panel (Tier 1 Testing)

Essential Tests to Rule Out Mimics

• Complete Blood Count (CBC): Screen for anemia, infection, and hematologic abnormalities that can present with motor symptoms 1, 2

• Comprehensive Metabolic Panel (CMP): Evaluate renal function, hepatic function, electrolytes, glucose, and calcium to identify metabolic disorders mimicking parkinsonism 1, 2

• Thyroid-Stimulating Hormone (TSH): Rule out hypothyroidism, which can cause bradykinesia, cognitive slowing, and tremor that mimic PD 1

• Vitamin B12 with metabolites: Measure serum B12 along with methylmalonic acid and homocysteine, as B12 deficiency causes peripheral neuropathy and motor dysfunction that can be confused with PD 1. Methylmalonic acid is more specific than homocysteine for B12 deficiency (98.4% vs 95.9% sensitivity) 1. Between 2.2-8% of patients with polyneuropathy have B12 deficiency based on elevated metabolites, and 44% of these have normal serum B12 levels 1.

• Ceruloplasmin and serum copper: Essential to exclude Wilson disease in patients under age 45, as this treatable condition presents with parkinsonism and psychiatric symptoms 1. An extremely low ceruloplasmin (<50 mg/L or 5 mg/dL) strongly suggests Wilson disease 1. Critical pitfall: Approximately 20% of heterozygotes have decreased ceruloplasmin, and normal ceruloplasmin does not exclude Wilson disease 1.

Context-Specific Additional Testing

When to Add Iron Studies

• Serum iron and ferritin: Consider in younger-onset PD patients, as research shows lower ceruloplasmin correlates with younger age of onset (≤60 years) 3. While not diagnostic, an inverse correlation exists between disease duration and serum iron/ferritin levels 4.

• Important caveat: Iron studies are not part of standard diagnostic workup but may provide prognostic information 5, 3, 4

When to Add Folate

• Serum folate: Order if B12 deficiency is suspected or if homocysteine is elevated, as folate deficiency also elevates homocysteine (91% of isolated folate deficiency cases) but not methylmalonic acid 1

What Laboratory Tests Cannot Do

Laboratory tests do not diagnose Parkinson's disease—PD remains a clinical diagnosis based on cardinal motor features (rest tremor, bradykinesia, rigidity, postural instability), response to levodopa, and exclusion of other causes 6, 7. No definitive diagnostic test or reliable biomarker exists for PD 6, 7.

Critical Clinical Pitfalls to Avoid

• Do not rely on laboratory abnormalities alone: Laboratory test results must be interpreted in the context of clinical information, as the etiologic yield of laboratory testing alone is limited by low specificity 1

• Do not assume normal ceruloplasmin excludes Wilson disease: Normal ceruloplasmin levels do not exclude Wilson disease, and modestly subnormal levels require further evaluation 1

• Do not order ceruloplasmin as a screening test without clinical suspicion: In one study of 2,867 patients with liver disease, only 1 of 17 with subnormal ceruloplasmin actually had Wilson disease (6% positive predictive value) 1

• Do not forget slit-lamp examination: If Wilson disease is suspected, Kayser-Fleischer rings should be sought by slit-lamp examination, though their absence does not exclude the diagnosis 1

Algorithmic Approach

1. First-line panel for all newly diagnosed PD patients: CBC, CMP, TSH, vitamin B12 with methylmalonic acid and homocysteine 1

2. Add ceruloplasmin and copper if: Patient is under age 45, has atypical features, psychiatric symptoms, or liver abnormalities 1

3. Consider iron studies if: Younger age of onset (≤60 years) or rapid progression 3, 4

4. Add folate if: Homocysteine is elevated but methylmalonic acid is normal, suggesting isolated folate deficiency 1

5. Pursue additional workup if: Laboratory abnormalities are found that could explain symptoms (e.g., very low ceruloplasmin warrants hepatic copper quantification and genetic testing for Wilson disease) 1