Indications for Testing

  • Excessive daytime sleepiness (EDS) with no known etiology occurring almost daily for ≥3 months

Laboratory Testing

  • Screening tests
    • CBC – rule out anemia as etiology of EDS
    • Random blood sugar (glucose) – rule out metabolic abnormality as etiology of EDS
  • Consider testing for drug abuse
  • Genetic testing – HLA typing
    • To determine presence of HLA-DQB1*06:02
      • Strongly associated with narcolepsy but by itself is not sufficient to cause narcolepsy
      • Highly sensitive in cases with cataplexy
      • More specific and sensitive than HLA-DR2, especially in African Americans
    • Consider melatonin testing – identify disruptions of the circadian rhythm

Other Testing

  • Polysomnography (PSG)
    • Overnight PSG followed by multiple sleep latency tests in the morning is diagnostic if positive
      • Positive test result – sleep latency ≤8 minutes plus the presence of REM sleep in at least 2 naps
  • Sleepiness scale (abbreviated)
  • Depression scale (abbreviated)
  • Symptom-based testing, such as emotion trigger of cataplexy and type of cataplexy

Differential Diagnosis

  • Adults
  • Children
    • Sleep disorders
      • Sleep-related breathing syndrome
      • Sleep depravation state
      • Idiopathic hypersomnia
      • Sleep apnea
    • Neurologic diseases
    • Drug/alcohol abuse
    • Other
      • Brain tumor

Clinical Background

Narcolepsy is a sleep disorder characterized by excessive daytime somnolence, cataplexy, sleep paralysis and hypnagogic hallucinations.


  • Incidence – 1/2,000
  • Age – first symptoms during teenage years; however, disorder is often not diagnosed for ≥10 years
  • Sex – M>F

Risk Factors

  • Family history of narcolepsy in first-degree relative increases risk by ten- to 40-fold
  • Genetics
    • HLA-DQB1*06:02 haplotype found in many patients
      • Associated with narcolepsy with cataplexy; >99% of patients with narcolepsy-cataplexy carry HLA-DQB1*06:02
      • Strongly associated with narcolepsy in the Japanese, African American, Korean, and Hispanic populations


  • Abnormality in hypocretin (orexin) neurotransmitter found in the hypothalamus
    • Hypocretins function to stimulate appetite and arousal; increases muscle tone during awake periods
    • Narcoleptics have very low levels of CSF hypocretin-1

Clinical Presentation

  • Tetrad – excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic hallucinations
    • Only 10-25% of patients display all four major symptoms
    • EDS – usually the first symptom
    • Cataplexy – sudden episode of muscle weakness; occurs in 60-70% of patients
      • Varies in severity – often triggered by emotion
      • Knees buckle (typical)
      • Diaphragm and oculomotor muscles are spared
      • No loss of consciousness
      • Duration – 30 seconds to as long as 2 minutes
    • Sleep paralysis – occurs most often while waking up; may also occur while falling asleep
      • Unable to move limbs, speak, or breathe deeply
    • Hypnagogic hallucinations – intense auditory or visual hallucinations at onset of sleep


  • Lifestyle modifications
  • Medications include modafinil for EDS, antidepressants and gamma hydroxybutyrate for cataplexy

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Narcolepsy (HLA-DQB1*06:02) Genotyping 2005023
Method: Polymerase Chain Reaction/Fluorescence Monitoring
Aids in clinical diagnosis of narcolepsy when other studies are inconclusive

Does not differentiate between heterozygosity and homozygosity of the HLA-DQB1*06:02 allele

Rare diagnostic errors may occur due to primer-site mutations

Alleles other than HLA-DQB1*06:02 will not be identified

Other genetic and nongenetic factors that influence narcolepsy are not evaluated

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Rule out anemia as etiology of excessive daytime sleepiness (EDS)

Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Rule out metabolic abnormality as etiology of EDS

Drugs of Abuse 9 Panel, Urine - Screen Only 0090453
Method: Qualitative Enzyme Multiplied Immunoassay Technique
Rule out drug abuse as etiology of EDS

Abuse is not confirmed by this test alone; additional panels, reflexed and directed drug confirmation testing in urine and serum/plasma also available

The following opioids are not detected in this test; fentanyl, buprenorphine, meperidine, tramadol, and tapentadol

Drug Screen (Nonforensic), Urine, Qualitative 0090500
Method: Qualitative Immunoassay/Gas Chromatography-Mass Spectrometry/Liquid Chromatography-Tandem Mass Spectrometry

Rule out drug abuse as etiology of EDS

Not optimized for most drugs of abuse; instead, refer to drug panel 9, 7, or 5

Melatonin 0098816
Method: Quantitative Radioimmunoassay

Identify disruptions of circadian rhythm