Presentations of Primary Hypersomnia in Chinese Children

Abstract

627Childhood Narcolepsy/Hypersomnia-Han et al on the pediatric population could help address issues related to puberty, genetic predisposition, and environmental triggers, and possibly shed light on factors that might delay diagnosis. We report on findings from a pediatric cohort of patients who presented with primary hypersomnia to a sleep clinic in Beijing, China over a period of ~10 years. All were evaluated in a standard fashion and classified as narcolepsy with or without cataplexy or idiopathic hypersomnia. Our purpose was to describe age of onset and clinical features of primary hypersomnia among a mainland Chinese cohort of children, and to compare the findings to the literature. METHODS PatientsPatients were children, defined as < 18 years of age, successively presenting with hypersomnia seen over a period of ~10 years (September, 1998 to May, 2009) at People's Hospital, Beijing University, Beijing. A total of 417 children (63%) were drawn from a population of 671 adults and children with hypersomnia. The hospital has a pulmonary medicine departmentbased sleep center, which sees both children and adults, and receives referrals from all of mainland China. It is estimated that 70% of the diagnosed narcolepsy patients in mainland China are seen at this center at People's Hospitals.12 A prior report focused on the impact of a narcolepsy recognition strategy in a pediatric neurology clinic, 13 whereas this report retrospectively describes a cohort with a broader symptom profile, evaluated using a stan- INTRODUCTIONNarcolepsy-cataplexy (NC) occurs worldwide. In China, there is a population prevalence of 0.034% in patients in South China presenting to sleep centers in Hong Kong 1,2 and a prevalence of 0.014% in Korean adolescents with similar clinical and biological presentations.3-5 Studies in North America and Europe estimates are similar. As the origin and mechanisms that produce narcolepsy are not well understood, comparisons of clinical presentations in collections of several characterized patient groups can inform future studies of clinical and genetic epidemiology.Narcolepsy-cataplexy is said to present in the second to third decade of life, with 70% to 80% of patients reporting onset between 10-20 years of age. Large sample size observations from the United States, Canada, Europe, and Japan report that half of adult patients with narcolepsy report narcolepsy onset prior to 15 years old, and only exceptionally at 5 or younger.6-9 Studies in the 1980s-1990s reported a median delay > 10 years between onset and diagnosis, 10 whereas a more recent report suggests the delay can be only a few years, particularly in children.11 A focus Objective: To retrospectively describe childhood presentations of primary hypersomnia with an emphasis on narcolepsy-cataplexy in a Chinese population. Methods: A total of 417 children (< 18 years old) successively presenting with complaints of hypersomnia without anatomic cause or sleep apnea risk were evaluated using the Stanford Sleep Inventory, human leukocyte antigen (HLA) ...

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

“…We also took advantage of the fact that most patients with narcolepsy diagnosed at Beijing are diagnosed rapidly after disease onset (most frequently as children, see Han et al [22]), and are untreated at the time of evaluation and diagnosis, allowing for a baseline measure of severity to compare the effects of genotypes at three loci on disease severity and age of onset.…”

“…Differences in HLA-DQ and TCRA frequencies across populations may thus contribute to differences in age of onset, or disease presentation. For example, our recent finding that disease onset has been reported to be younger in Chinese versus Caucasian children [22], where the AA genotype is the most frequent in the general population (58% in Caucasians see Hallmayer et al 8 ., versus 21% in Chinese, see Table 1) and DQB1*0602 frequency is as high as in Caucasians. Several authors have also pointed out that in Caucasians the distribution of age of onset is bimodal, with a second peak of onset after age 30, a phenomenon not reported in Japan, another population with low rs1154155A frequency [28,29].…”

“…In prior studies, we estimated that around 70% of all diagnosed narcolepsy patients in China have been evaluated at Beijing University in our laboratory [21]. A description of these subjects and evaluation procedures are reported in Han et al [22]. Age of onset of disease was defined as the earliest of cataplexy or sleepiness.…”

Genome Wide Analysis of Narcolepsy in China Implicates Novel Immune Loci and Reveals Changes in Association Prior to Versus After the 2009 H1N1 Influenza Pandemic

“…To identify novel narcolepsy susceptibility loci potentially missed in previous studies focused on European ancestry, we studied 1,189 Chinese narcolepsy cases primarily characterized at a single clinical center (Beijing University) [9], [18], [21] and 1,997 Chinese controls genotyped on the Affymetrix Axiom CHB array. All cases had documented hypocretin deficiency or had clear-cut cataplexy and HLA DQB1*06:02, ensuring etiological homogeneity and meeting ICSD3 criteria for type 1 narcolepsy.…”

La narcolepsie avec cataplexie : une maladie auto-immune ?

“…En effet, si une association a bien été retrouvée entre la narcolepsie de type 1 et le vaccin H1N1, aucune association n'a été mise en évidence entre la narcolepsie et les autres vaccinations, ni avec les épisodes infectieux grippaux ou non survenus depuis le 1 er janvier 2005. Outre les différences d'effectifs dans les deux études, il est probable que les populations française et chinoise ne soient pas identiques en termes de susceptibilité vis-à-vis de la narcolepsie, car la maladie se révèle à un plus jeune âge en Chine [37]. Dans le cas de l'infection à Streptococcus pyogenes, les marqueurs spécifiques de cette infection, anticorps anti-streptolysine 0 et anti-Dnase B, sont significativement plus élevés chez les patients narcoleptiques que chez les contrôles, et ce d'autant plus que le diagnostic de narcolepsie est récent [38].…”