BACKGROUND: Narcolepsy is a neurologic disorder characterized by excessive daytime sleepiness, symptoms of abnormal rapid eye movement (REM) sleep, and a strong association with HLA-DRB1*1501, -DQA1*0102, and -DQB1*0602. Here, we investigated the clinico-physical characteristics of Korean patients with narcolepsy, their HLA types, and the clinical utility of high-resolution PCR with sequence-specific primers (PCR-SSP) as a simple typing method for identifying DRB1*15/16, DQA1, and DQB1 alleles. METHODS: The study population consisted of 67 consecutively enrolled patients having unexplained daytime sleepiness and diagnosed narcolepsy based on clinical and neurological findings. Clinical data and the results of the multiple sleep latency test and polysomnography were reviewed, and HLA typing was performed using both high-resolution PCR-SSP and sequence-based typing (SBT). RESULTS: The 44 narcolepsy patients with cataplexy displayed significantly higher frequencies of DRB1*1501 (Pc= 0.003), DQA1*0102 (Pc=0.001), and DQB1*0602 (Pc=0.014) than the patients without cataplexy. Among patients carrying DRB1*1501-DQB1*0602 or DQA1*0102, the frequencies of a mean REM sleep latency of less than 20 min in nocturnal polysomnography and clinical findings, including sleep paralysis and hypnagogic hallucination were significantly higher. SBT and PCR-SSP showed 100% concordance for high-resolution typing of DRB1*15/16 alleles and DQA1 and DQB1 loci. CONCLUSIONS: The clinical characteristics and somnographic findings of narcolepsy patients were associated with specific HLA alleles, including DRB1*1501, DQA1*0102, and DQB1*0602. Application of high-resolution PCR-SSP, a reliable and simple method, for both allele- and locus-specific HLA typing of DRB1*15/16, DQA1, and DQB1 would be useful for characterizing clinical status among subjects with narcolepsy.
Adolescent ; Adult ; Aged ; Alleles ; Cataplexy/genetics ; *DNA Probes, HLA ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; HLA-DQ Antigens/genetics ; HLA-DRB1 Chains/genetics ; *Histocompatibility Testing ; Humans ; Male ; Middle Aged ; Narcolepsy/*diagnosis/genetics ; Phenotype ; Polymerase Chain Reaction

OBJECTIVENarcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, and features of rapid eye movement (REM) sleep, such as cataplexy, sleep paralysis and hypnagogic hallucinations. The present study aimed to investigate the diagnostic basis of childhood narcolepsy and possible role of HLA Class II alleles in the onset of this disease.

METHODSThe clinical data of 40 narcoleptic children were analyzed. All patients received Multiple Sleep Latency Test (MSLT) and they were analyzed in combination with clinical features. Polymerase chain reaction/sequence specific primers (PCR/SSP) methods were used to detect the HLA-DRB1 and DQB1 alleles.

RESULTSNarcolepsy was diagnosed in 40 children. The age range was 3 to 14 years (mean 8.5 +/- 2.5 years), 29 were male and 11 female. Their mean course of disease was 6.5 months, 14 patients (30%) were less than 3 months old, 21 patients (52%) were less than 6 months old. All the patients had excessive daytime sleepiness, cataplexy appeared in 37 cases, hypnagogic hallucination in 22 and sleep paralysis in 6. Mean sleep latency on MSLT was less than 5 min, the average number of sleep-onset rapid eye movement (SOREM) was 4.33 +/- 0.26 episodes (2-5 episodes), the latency of SOREM episodes were 4.0 +/- 1.8 min (0.25-4.9 min). Thirty-five patients were DRB1 1501 and DQB1 0602 positive (Pc < 0.01), 2 were DRB1 1502 and DQB1 0601 positive, while 3 were DRB1 15 and DQB1 6 negative.

CONCLUSIONSSome pediatric patients with narcolepsy were different from adult patients in that the pediatric cases had a sudden onset and shorter disease course. Diagnosis of this disease was based on the clinical manifestations, MSLT and absence of any medical or psychiatric disorder that could account for the symptoms. The authors demonstrated that DRB1 1501 and DQB1 0602 were susceptibility genes for narcolepsy and those who were DRB1 15 negative could not be excluded.

Adolescent ; Child ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; genetics ; HLA-DQ Antigens ; genetics ; HLA-DQ beta-Chains ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Humans ; Infant ; Male ; Narcolepsy ; diagnosis ; genetics ; physiopathology ; Polymerase Chain Reaction