Correlation between HLA-DQB1*06:02 and narcolepsy with and without cataplexy: approving a safe and sensitive genetic test in four major ethnic groups. A systematic meta-analysis.

STUDY OBJECTIVES: we performed a meta-analysis to assess the usefulness of HLA testing for Narcolepsy diagnosis in four major ethnical groups: Asians, Afro-Americans, Amerindians and Caucasians. METHODS: PubMed, EMBASE, Web of Science, Scopus and Cochrane databases were searched for articles in English and French published before October 2017 on HLA class II alleles in Narcolepsy. We included case-control studies, cross-sectional and retrospective cohort studies with patients diagnosed following the International classifications of sleep disorders (1990-2012) and ethnically matched controls. Following PRISMA guidelines, two investigators independently extracted data according to the inclusion criteria listed in PROSPERO CRD42017058677. A third researcher was consulted for discrepancies. We extracted and pooled adjusted OR using random-effect models. We verified the strength of the association between HLA-DQB1*06:02 and the worldwide distribution of Narcolepsy type 1 (NT1) and type 2 (NT2); furthermore, we pooled the OR measuring the association between HLA-DQB1*06:02 and NT1, NT2 and hypersomniacs. RESULTS: We identified 511 titles. Of these, 12 case-control studies were included, for a total of 2077 NT1 patients, 235 NT2 patients, 161 hypersomniacs and 7802 controls. In the population-stratified analysis, HLA-DQB1*06:02 conferred an increased risk for NT1 (OR: 24.1, IC: 14.6-39.5, p < 0.001) and NT2 (OR: 3.9; IC: 2.2-6.8, p < 0.001). For NT1 the pooled estimated positive Likelihood Ratio (LR+) was 5.94 (IC: 3.71-9.51) and the negative Likelihood Ratio (LR-) was 0.23 (IC: 0.16-0.33); for NT2 LR+ was 3.35 (IC: 2.08-5.38) and LR- 0.72 (IC: 0.63-0.81). Moreover, for hypersomniacs LR+ was 1.436 (IC 0.668-3.089) and LR- 0.903 (IC 0.714-1.142). CONCLUSIONS: Our data support the preponderant role of HLA-DQB1*06:02 in susceptibility to NT1/NT2 across all ethnicities. HLA-DQB1*06:02 negativity should make clinicians cautious in excluding other diagnoses.

The Prevalence and Characteristics of Primary Headache and Dream-Enacting Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi-Centre Cross-Sectional Study.

BACKGROUND: Because the prevalence and characteristics of primary headache have yet to be thoroughly studied in patients with hypersomnia disorders, including narcolepsy and idiopathic hypersomnia, we examined these parameters in the Japanese population. METHODS: In a multicentre cross-sectional survey, among 576 consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35 idiopathic hypersomnia patients were included. Additionally, 61 healthy control subjects participated. Semi-structured headache questionnaires were administered to all participants. RESULTS: The patients with narcolepsy (52.9%) and idiopathic hypersomnia (77.1%) more frequently experienced headache than the healthy controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type headache among the narcolepsy patients, the idiopathic hypersomnia patients and the control subjects, respectively. Those who experienced migraine more frequently experienced excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of ≥10, than those who did not experience headache among the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as evaluated by the rapid eye movement sleep disorders questionnaire, was more frequently observed in the narcolepsy patients than in the idiopathic hypersomnia patients and the control subjects. An increased DEB frequency was observed in the narcolepsy patients with migraines compared to those without headache. CONCLUSIONS: Migraines were frequently observed in patients with narcolepsy and idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further studies are required to assess the factors that contribute to migraines in narcolepsy and idiopathic hypersomnia patients.

Association analysis of the major histocompatibility complex, class II, DQ ß1 gene, HLA-DQB1, with narcolepsy in Han Chinese patients from Taiwan.

BACKGROUND: Narcolepsy is a rare, chronic, disabling neuropsychiatric disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and abnormal rapid eye movement sleep. It is strongly associated with the HLA-DQB1(∗)06:02 allele in various ethnic groups. Our study aimed to investigate the allelic spectrum of HLA-DQB1 in a sample of Han Chinese patients with narcolepsy and control subjects from Taiwan. METHODS: We determined the genotype of the major histocompatibility complex, class II, DQ ß1 gene, HLA-DQB1, in 72 narcolepsy subjects (44 men, 28 women), including 52 narcolepsy subjects with cataplexy (narcolepsy+cataplexy), 20 narcolepsy subjects without cataplexy (narcolepsy-cataplexy), and 194 control subjects (94 men, 100 women) using a sequence-specific oligonucleotide-probe hybridization technique. RESULTS: We found a strong HLA-DQB1(∗)06:02 association in narcolepsy+cataplexy subjects (odds ratio [OR], 321.4 [95% confidence interval {CI}, 70.7-1461.4]). The association was less prominent in narcolepsy-cataplexy subjects (OR, 6.9 [95% CI, 2.4-20.1]). In addition to the DQB1(∗)06:02, we found that (∗)03:01 also was a predisposing allele (OR, 2.0 [95% CI, 1.1-3.7]) in narcolepsy+cataplexy subjects, though the (∗)06:01 was a predisposing allele (OR, 2.8 [95% CI, 1.2-6.7]) in narcolepsy-cataplexy subjects. Furthermore, we found a significant overrepresentation of DQB1(∗)06:02 homozygotes in narcolepsy+cataplexy subjects. CONCLUSIONS: Our data add further support to the strong association of the HLA-DQB1(∗)06:02 allele with narcolepsy, especially in narcolepsy+cataplexy patients. Our study also indicates additional HLA-DQB1 alleles may modify the presentation of narcolepsy+cataplexy patients, such as DQB1(∗)03:01 and DQB1(∗)06:01 in our study. Our results are limited by the small sample size and can only be considered as preliminary findings.

Hypocretin (orexin) neuropeptide precursor gene, HCRT, polymorphisms in early-onset narcolepsy with cataplexy.

BACKGROUND: To test if the hypocretin (orexin) neuropeptide precursor (HCRT) gene, HCRT, mutations are implicated in the development of narcolepsy with cataplexy deficiency in young children. METHODS: The entire HCRT gene and ~2000 bp promoter region was first sequenced in 181 patients and 153 controls, and rare polymorphisms including three nonsynonymous amino acid changes were identified. Next the 557 bp region of exon 2 harboring the three nonsynonymous changes was sequenced in an additional 298 early-onset subjects and in 148 control samples. RESULTS: A previously known common polymorphism (rs760282) and nine rare novel polymorphisms were identified in subjects and controls without significant differences. Two nonsynonymous exon 2 substitutions (+977 H54A, +979 G55R) were detected in two subjects with early onset at 7 and 6 years, respectively, but were not found in any controls. These substitutions are not likely to vastly change peptide binding to hypocretin receptors. One additional exon 2 substitution (+1019, K68R) was found in two patients and one control. Additional sequencing that focused on exon 2 showed additional subjects and controls with the +1019 K68R polymorphism and without significant differences between the subjects and the control. Segregation of two of these three nonsynonymous single nucleotide polymorphisms (SNPs) were observed from unaffected parents to offspring. CONCLUSIONS: Sequencing of a large number of early-onset narcolepsy subjects revealed three novel nonsynonymous substitutions within the preprohypocretin protein, two of which were only found in patients with early-onset narcolepsy but are not likely to be functionally significant, especially in heterozygote subjects.

TCRA, P2RY11, and CPT1B/CHKB associations in Chinese narcolepsy.

OBJECTIVES: Polymorphisms in the TCRA and P2RY11, two immune related genes, are associated with narcolepsy in Caucasians and Asians. In contrast, CPT1B/CHKB polymorphisms have only been shown to be associated with narcolepsy in Japanese, with replication in a small group of Koreans. Our aim was to study whether these polymorphisms are associated with narcolepsy and its clinical characteristics in Chinese patients with narcolepsy. METHODS: We collected clinical data on 510 Chinese patients presenting with narcolepsy/hypocretin deficiency. Patients were included either when hypocretin deficiency was documented (CSF hypocretin-1≤110 pg/ml, n=91) or on the basis of the presence of clear cataplexy and HLA-DQB1∗0602 positivity (n=419). Genetic data was compared to typing obtained in 452 controls matched for geographic origin within China. Clinical evaluations included demographics, the Stanford Sleep Inventory (presence and age of onset of each symptom), and Multiple Sleep Latency Test (MSLT) data. RESULTS: Chinese narcolepsy was strongly and dose dependently associated with TCRA (rs1154155C) and P2RY11 (rs2305795A) but not CPT1B/CHKB (rs5770917C) polymorphisms. CPT1B/CHKB polymorphisms were not associated with any specific clinical characteristics. TCRA rs1154155A homozygotes (58 subjects) had a later disease onset, but this was not significant when corrected for multiple comparisons, thus replication is needed. CPT1B/CHKB or P2RY11 polymorphisms were not associated with any specific clinical characteristics. CONCLUSIONS: The study extends on the observation of a strong multiethnic association of polymorphisms in the TCRA and P2RY11 with narcolepsy, but does not confirm the association of CPT1B/CHKB (rs5770917) in the Chinese population.

The reliability and validity of the Korean version of the Pittsburgh Sleep Quality Index.

PURPOSE: The Pittsburgh Sleep Quality Index (PSQI) is a self-reported questionnaire that measures sleep quality during the previous month. The aims of this study were to analyze the reliability and validity of the Korean version of the PSQI (PSQI-K) and to evaluate its usefulness. METHODS: We developed the PSQI-K, which involved translating the original PSQI into Korean and then translating back into English to check its accuracy. We tested the validity of the PSQI-K on a total of 394 individuals: 261 with poor sleep (primary insomnia, n = 211; narcolepsy, n = 50) and 133 with good sleep. All subjects completed the PSQI-K, 285 had overnight nocturnal polysomnography, and 53 were randomly selected for a retest with the questionnaire after 2-4 weeks without any intervening treatment. The mean PSQI-K global scores in each group were analyzed after adjusting for age and sex. RESULTS: Cronbach's α coefficient for internal consistency of the total score of the PSQI-K was 0.84 which shows high reliability. Sensitivity and specificity for distinguishing poor and good sleepers were 0.943 and 0.844 using the best cutoff point of 8.5. The total and component scores of the PSQI-K for insomnia and narcolepsy were significantly higher than those for controls (p < 0.05). The test-retest correlation coefficient was 0.65 for the total score (p < 0.001). There was no significant difference between the two values using the paired t tests. CONCLUSIONS: The PSQI-K is a reliable and valid questionnaire for evaluating sleep quality in patients with sleep disorders.

Quality of life in patients with narcolepsy with cataplexy, narcolepsy without cataplexy, and idiopathic hypersomnia without long sleep time: comparison between patients on psychostimulants, drug-naïve patients and the general Japanese population.

OBJECTIVE: To assess the quality of life of patients with narcolepsy with cataplexy (NA-CA), narcolepsy without cataplexy (NA w/o CA), and idiopathic hypersomnia without long sleep time (IHS w/o LST) who were taking psychostimulant medication, and to ascertain which factors (including psychosocial and environmental variables) influence quality of life in this population. METHODS: In total, 185 patients who had received regular treatment were enrolled in the study (NA-CA, n=83; NA w/o CA, n=48; IHS w/o LST, n=54). Patients were asked to complete questionnaires including the Short Form-36 Health Survey (SF-36), the Epworth Sleepiness Scale (ESS), and items concerning psychosocial and environmental variables. RESULTS: All three diagnostic groups had significantly lower scores for most SF-36 domains compared with the Japanese normative data, and the ESS score was significantly reduced with treatment. Multiple logistic regression analyses revealed that several SF-36 domains were associated with the ESS score; autonomy in controlling own job schedule, experience of divorce or break up with a partner due to symptoms, experience of being forced to relocate or being dismissed due to symptoms, and perception of support from others. CONCLUSIONS: The severity of subjective sleepiness and psychological and environmental variables influenced quality of life in patients with these hypersomnias of central origin.

Low vitamin D in narcolepsy with cataplexy.

BACKGROUND: Narcolepsy with cataplexy (NC) is currently thought to be an autoimmune-mediated disorder in which environmental risk factors make a significant contribution to its development. It was proposed that vitamin D deficiency plays a role in autoimmune diseases. Here we investigated whether NC can be associated with 25-hydroxyvitamin D (25(OH)D) level deficiency in patients with NC compared with gender- and age-matched normal controls. METHODOLOGY: Serum level of 25 (OH)D was determined in 51 European patients with typical NC compared to 55 age-, gender-, and ethnicity-matched healthy controls. Demographic and clinical data (age at onset, duration and severity of disease at baseline, and treatment intake at time of study) and season of blood sampling were collected to control for confounding variables. PRINCIPAL FINDINGS: Serum 25(OH)D concentration was lower in NC compared to controls (median, 59.45 nmol/l [extreme values 24.05-124.03] vs. 74.73 nmol/l [26.88-167.48] p = 0.0039). Patients with NC had significantly greater vitamin D deficiency (<75 nmol/l) than controls (72.5% vs 50.9%, p = 0.0238). Division into quartiles of the whole sample revealed that the risk of being affected with NC increased with lower 25(OH)D level, with a 5.34 OR [1.65-17.27] for the lowest quartile (p = 0.0051). Further adjustment for BMI did not modify the strength of the association (OR: 3.63, 95% CI = 1.06-12.46, p = 0.0191). No between BMI and 25(OH)D interaction, and no correlation between 25(OH)D level and disease duration or severity or treatment intake were found in NC. CONCLUSION: We found a higher frequency of vitamin D deficiency in NC. Further studies are needed to assess the contribution of hypovitaminosis D to the risk of developing narcolepsy, and to focus on the utility of assessing vitamin D status to correct potential deficiency.

Prevalence of narcolepsy in King County, Washington, USA.

BACKGROUND: Relatively few epidemiologic studies have focused on narcolepsy, a disabling sleep disorder with a strong association with HLA-DQB1 *0602. METHODS: We sought to estimate the prevalence of narcolepsy using multiple overlapping techniques to identify residents of King County, WA who were 18 years or older with physician-diagnosed narcolepsy. Patients were entered into a registry and recruited into an epidemiologic study entailing interview and buccal scrapings to determine HLA-DQB1 *0602 status. Missing values were imputed to allow prevalence to be estimated based on all 425 patients entered into the registry between 2001 and 2005, whether they were recruited into the epidemiologic study (n=279) or not (n=146). RESULTS: As of July 01, 2001, estimated prevalence per 100,000 of physician-diagnosed narcolepsy with cataplexy was 21.8 (95% confidence interval (CI): 18.8-24.8), similar to prior studies. The median age of onset was 14 (interquartile range: 10-18). For narcolepsy with HLA-DQB1 *0602, prevalence was 15.3 (95% CI: 12.8-17.9). Estimated prevalence was higher in women than men and in African-Americans than other racial groups. CONCLUSIONS: These differences could reflect problems in identification and recruitment or may provide etiologic clues about narcolepsy. This study illustrates the challenges in performing population-based studies of narcolepsy.

The familial risk and HLA susceptibility among narcolepsy patients in Hong Kong Chinese.

STUDY OBJECTIVES: To explore the familial aggregation and HLA susceptibility of narcolepsy in Hong Kong Chinese by objective sleep measurements and HLA typing. DESIGN: Case control design PARTICIPANTS: Twelve narcoleptic probands, 34 first-degree relatives, and 30 healthy controls. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Each subject underwent a standardized nocturnal polysomnogram (PSG), followed by a daytime multiple sleep latency test (MSLT). HLA typing was performed for all subjects. One relative (2.9%) was diagnosed as suffering from narcolepsy with cataplexy. Nearly 30% of the relatives fulfilled the criteria of narcolepsy spectrum disorder (shortened mean sleep latency [MSL] and/or the presence of sleep onset REM periods [SOREMPs]). When using the population data for comparison, the relative risk of narcolepsy in first-degree relatives was 85.3. The odds ratio of narcolepsy spectrum disorder in first-degree relatives was 5.8 (95% CI: 1.2 - 29.3) when compared to healthy controls. There existed 6 multiplex families, in which all 10 relatives with narcolepsy spectrum disorders, including all 3 relatives with multiple SOREMPs, were positive for HLA DQB1*0602. CONCLUSIONS: Our study demonstrated a definitive familial aggregation of narcolepsy, narcolepsy spectrum disorders, and possibly cataplexy in Hong Kong Chinese. This familial aggregation supported an inherited basis for narcolepsy spectrum. The tight co-segregation of HLA DQB1*0602 and narcolepsy spectrum disorders might suggest that HLA typing, especially DQB1*0602, at least partly confer the familial risk of narcolepsy. In addition, our study suggested that the subjective questionnaire measurements including Ullanlinna Narcolepsy Scale and Epworth Sleepiness Scale were unable to detect the presence of narcolepsy spectrum disorders among the relatives. A stringent objective measurement-based design for family studies is suggested for future study. Further studies are indicated for the determination of the mode and molecular level of narcolepsy transmission.

Clinical and neurobiological aspects of narcolepsy.

Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy and/or other dissociated manifestations of rapid eye movement (REM) sleep (hypnagogic hallucinations and sleep paralysis). Narcolepsy is currently treated with amphetamine-like central nervous system (CNS) stimulants (for EDS) and antidepressants (for cataplexy). Some other classes of compounds such as modafinil (a non-amphetamine wake-promoting compound for EDS) and gamma-hydroxybutyrate (GHB, a short-acting sedative for EDS/fragmented nighttime sleep and cataplexy) given at night are also employed. The major pathophysiology of human narcolepsy has been recently elucidated based on the discovery of narcolepsy genes in animals. Using forward (i.e., positional cloning in canine narcolepsy) and reverse (i.e., mouse gene knockout) genetics, the genes involved in the pathogenesis of narcolepsy (hypocretin/orexin ligand and its receptor) in animals have been identified. Hypocretins/orexins are novel hypothalamic neuropeptides also involved in various hypothalamic functions such as energy homeostasis and neuroendocrine functions. Mutations in hypocretin-related genes are rare in humans, but hypocretin-ligand deficiency is found in many narcolepsy-cataplexy cases. In this review, the clinical, pathophysiological and pharmacological aspects of narcolepsy are discussed.

Daytime sleepiness with and without cataplexy in Chinese-Taiwanese patients.

BACKGROUND AND PURPOSE: Investigation of Chinese-Taiwanese patients with excessive sleepiness, but no association with other sleep disorders, and with the presence or absence of cataplexy. PATIENTS AND METHODS: Thirty-five patients, successively referred between 2002 and 2004, underwent polysomnography (PSG), repeat multiple sleep latency test (MSLT), and human leukocyte antigen (HLA) typing. Three patients without cataplexy also had cerebrospinal fluid (CSF) hypocretin measurements. RESULTS: DQB1*0602 was associated with cataplexy in over 90% of Chinese-Taiwanese cases. Absence of cataplexy and <2 sleep-onset REM periods (SOREMPs) was seen in only two subjects, but presence of two SOREMPs did not dissociate DQB1*0602 positive and negative or cataplexy positive and negative subjects. As a group, narcoleptics with cataplexy had a higher number of SOREMPs, and the mean sleep latency was much shorter in narcoleptics with cataplexy than in the non-cataplectic patients, independent of the number of SOREMPs. CONCLUSIONS: Chinese-Taiwanese patients with cataplexy present with similar HLA findings as Black and Caucasian patients, but the presence of two or more SOREMPs in Chinese-Taiwanese patients is not a sufficient diagnostic tool to identify narcolepsy. When cataplexy is not present, description of PSG nd HLA findings may be a better approach than using a label with little scientific significance, allowing for better collection of patients' phenotype.

The prevalence of narcolepsy among Chinese in Hong Kong.

Narcolepsy is a lifelong, crippling sleep disorder. Although the discovery of the hypocretin system has been a breakthough in genetics, the epidemiological aspects of narcolepsy remain elusive. Ethnic predisposition was suggested to partially account for the 2,500-fold difference in the reported prevalence rates of narcolepsy between Japanese (0.59%) and Israeli Jews (0.00023%). We carried out a general population study, conducting a random telephone survey with a structured questionnaire, which included a validated screening instrument (a Chinese version of the Ullanlinna Narcolepsy Scale). It was followed by clinical-polysomnographic-HLA confirmation of the subjects determined to be positive for narcolepsy based on the questionnaire. Of 9,851 subjects interviewed, 28 subjects (0.28%, 58% female) were screened positive. Ninety percent had a second detailed interview, 64% had HLA typing, and over half of them had a sleep assessment. Only three subjects were found to have genuine narcolepsy. The most common nonnarcolepsy diagnoses were sleep apnea syndrome and sleep-wake schedule disorder. The prevalence rate of narcolepsy in Southern (Hong Kong) Chinese was found to be 0.034% (95% confidence interval = 0.010-0.117%). All available narcoleptic subjects were HLA DRB1-1501 positive and 50% were DQB1-0602 positive. The prevalence rate of narcolepsy among Chinese is comparable to the rates for other populations in studies with stringent epidemiological designs, suggesting that major cross-ethnic differences in the prevalence rates of narcolepsy previously reported likely resulted from methodological limitations.

A validity study of Ullanlinna Narcolepsy Scale in Hong Kong Chinese.

OBJECTIVE: To validate the Chinese version of Ullanlinna Narcolepsy Scale (CUNS). METHODS: A total of 234 subjects [163 male (69.7%) and 71 female (30.3%)] including 17 patients with narcolepsy, 21 normal controls and 196 patients with various sleep and psychiatric disorders were studied. The diagnoses of these patients were independently ascertained with sleep laboratory confirmation whenever indicated. All the subjects were interviewed through the telephone by a trained lay interviewer who was blind to the diagnosis. The questionnaire included demographic information, sleep habits and CUNS. RESULTS: Narcoleptic patients had a significantly higher CUNS score (18.6+/-4.7; 95% confidence interval (CI) 16.2-21.0) and differentiated well from all the other groups (F(6,227)=28.4, P<0.001). The CUNS has a satisfactory internal consistency with Cronbach's alpha of 0.75. The principal component analysis with varimax rotation revealed two factors, namely sleepiness and cataplexy factors, which accounted for 45.5% of the total variance. The best cut-off point for the CUNS scale was found to be at 13/14 with high specificity (93.5%), sensitivity (94.1%), negative predictive value (NPV, 99.5%) and modest positive predictive value (PPV, 53.3%). The AUC of receiver operating characteristic (ROC) analysis was 0.97 (95% CI 0.95-0.99). CONCLUSIONS: The CUNS was validated with satisfactory psychometric properties. The cross-cultural validation of UNS scale suggested that it could be used across the ethnic groups.

HLA DR2 and DQ1 frequency among narcoleptic patients in Hong Kong Chinese.

Narcolepsy is a life-long crippling sleep disorder with significant physical and psychosocial impairments. Although its exact etiology and neuropathology is not clear, a strong association with specific human leucocyte antigen (HLA) subtype, particularly DR2 (DRw15) and DQw1 (DQw6), has been demonstrated across different ethnic groups including Caucasians and Japanese. The presence of 100% association with HLA DR2 in a series of Hong Kong Chinese narcoleptic patients has previously been reported. The report can now be extended, and as far as could be ascertained in the available subjects, all were HLA DQw1 (DQw6)-positive. This is concordant with the experiences of Japanese narcoleptic patients who are 100% HLA DR2- and DQw1-positive. However, the definitive account of the population prevalence of narcolepsy in Chinese could be determined only by a well-conducted epidemiological study with laboratory confirmation.

Narcolepsy in Hong Kong Chinese--a preliminary experience.

BACKGROUND: Narcolepsy is a sleep disorder of unknown aetiology. Despite the widely reported strong association with HLA DR2 among different ethnic groups and their varying prevalence rates, there has never been any series of laboratory documented narcolepsy in Chinese. AIMS: To report the preliminary experience with Chinese narcoleptic patients and their HLA typing. METHODS: The records of 342 patients who presented to our sleep laboratory for various sleep problems from 1986 to 1992 were examined. Both clinical and polysomnographic data were analysed. The criteria for a diagnosis of narcolepsy is based on shortened mean sleep latency of less than 5 minutes and presence of rapid eye movement (REM) sleep in two or more of the five 20-minute naps during multiple sleep latency test (MSLT). RESULTS: There were five narcoleptic patients documented resulting in an overall laboratory prevalence of 1.5% or 2.3% of patients presenting with hypersomnia. All patients were HLA DR2 positive. CONCLUSION: There is 100% association with HLA DR2 in Hong Kong Chinese narcoleptic patients. Based on the laboratory prevalence, the prevalence rate of narcolepsy among Hong Kong Chinese population is estimated to be within the range of four in 10,000 to one in 100,000.

HLA-DR2 negative narcolepsy in Australian Caucasians: clinical features, serology and sequence specific oligonucleotide typing.

An almost invariable association with HLA-DR2 and DQw1 has previously been reported in Japanese and caucasian narcoleptics. We performed HLA typing in 18 Australian narcoleptics using serological techniques and sequence specific oligonucleotide probes. HLA-DQw1 was present in 15 patients and DR2 in 12; 3 patients with cataplectic narcolepsy were DR2-negative. The serological haplotype most strongly associated with narcolepsy was DRw15 (a subtype of DR2), DQw1. DRw15-positive patients were positive for the alleles DRB1*1501 and DQB1*0602 defined with oligonucleotide probes. We conclude that the association of narcolepsy with DR2 and DQw1 is not as strong as previously reported and the absence of DR2 or DQw1 does not preclude the diagnosis of classical narcolepsy, at least in caucasians. Secondly, DR2-positive narcoleptics possess characteristic serological subtypes and alleles defined with oligonucleotide probes that are also found in normals. Thirdly, the occurrence of DR2-negative cataplectic narcoleptics points to the existence of more than one narcolepsy susceptibility gene.