Narcolepsy is a chronic, debilitating sleep disorder which is characterized by cataplexy (i.e. sudden transient muscular weakness), sleep paralysis, disturbed night sleep and excessive daytime sleepiness.
Narcolepsy is caused by deficiencies in the hypothalamic neurotransmitter, hypocretin (also known as orexin), most likely through autoimmune-mediated cell death of the neurons producing this neurotransmitter. Hypocretin is a neuropeptide hormone that is responsible for controlling appetite and sleep patterns.
Patients are typically booked for a sleep study to establish breathing, heart rate, brain activity, and other bodily functions during the night to determine abnormal patterns of sleep. Laboratory tests to diagnose narcolepsy are dependent on analysis of orexin levels in the cerebrospinal fluid (CSF), which requires a highly invasive and painful lumbar puncture.
Genetics can play an important role in certain patients with narcolepsy. One important predisposing genetic factor is the HLA-DQB1*06:02 allele in the DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype. Between 85 to 95 percent of narcoleptics with the symptom of sudden muscle weakness have this combination of alleles. HLA-DQB1*06:02 genotyping, can be particularly useful in helping to diagnose patients with the symptom of sudden muscle weakness with narcolepsy.