0648 NARCOLEPSY SPECTRUM DISORDER IN 378 PARENTS OF PATIENTS WITH TYPE 1 NARCOLEPSY-CATAPLEXY

Abstract

To evaluate familial risk of narcolepsy in parents of children with Type 1 narcolepsy using objective sleep recording studies. From a total of 5,462 patient visiting the Sleep Center of Peking University People’s Hospital from 09/01/2012 to 12/03/2014, 496 narcolepsy cases were identified, including 307 children meeting inclusion criteria (<18 y, HLA-DQB1*0602 positive, typical cataplexy, or measured CSF Hcrt ≤ 110 pg/ml). One hundred and six families refused further evaluation or had parent(s) unavailable, leaving 201 families (66%) with at least one parent available. The resulting 378 parents underwent HLA typing, nocturnal polysomnography, multiple sleep latency tests(MSLT), interviews and questionnaire evaluation. CSF hypocretin-1 was tested in 4 subjects. Three subjects with a positive MSLT had a second MSLT for confirmation. ICSD3 criteria were used to diagnose Type 1 and Type 2 narcolepsy. Symptoms in parents with versus without DQB1*06:02 were also compared. We found 3 parents (0.7%) with narcolepsy- cataplexy (100% DQB1*06:02) and 9 with a positive MSLT but no cataplexy (78% DQB1*06:02). In the four parents tested for CSF hypocretin-1 level, one with and one without cataplexy had low CSF Hcrt (≤110) one without cataplexy had intermediary level(153 pg/ml), and normal in the last relative. Repeat PSG-MSLT was positive in 3 relatives retested. Analysis of individual patients suggests that between 3 (0.7%) and 6 (1.4%) of the 9 subjects with narcolepsy-cataplexy have hypocretin deficiency. This study is the first to confirm the existence of a genuine narcolepsy/hypocretin deficiency spectrum using systematic MSLT testing, HLA typing and CSF hypocretin-1 measurements in a very large number of relatives of patients with Type 1 narcolepsy. These findings illustrate the urgent need to find biologically measurable immune markers for the disease autoimmune process, as this would greatly facilitate large population based studies and a better understanding of its spectrum. Supported by NSFC (81300061,81420108002, 81670087),Ministry of Science and Technology (2015CB856405, 2014DFA31500)Corresponding to: hanfang1@hotmail.com;mignot@stanford.edu