ESPE Abstracts

Background: ROHHAD/ROHHADNET syndrome (rapid-onset obesity with hypothalamic dysfunction, central hypoventilation, autonomic dysregulation with or without neural tumor - NET) – has been reported in association with cerebral venous thrombosis events, as reported also in central hypoventilation syndrome. It is not clear whether thrombotic risk represents a cause or a consequence of hypoventilation and hypothalamic dysfunction. Aim of our study was to characterize thrombotic risk and endothelial damage in ROHHAD/ROHHADNET patients.

Patients and Methods: We analyzed clinical, biochemical and EndoPAT® data from 14 patients with ROHHAD syndrome (4M, 10F), followed at a single centre (Pediatric Endocrinology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy). ROHHAD diagnosis was based on the presence of at least 3 of the following criteria: early, rapid-onset obesity, central hypoventilation, neural tumor, hypothalamic/pituitary disorders, and autonomic dysfunction, after excluding other forms of syndromic obesity. Biochemical data and thrombotic risk profile included levels of PT(%), PTT(sec), Fibrinogen(mg/100mL), Factor VIII(%), von Willebrand’s factor(%), Antithrombin(%), Protein C(%), Protein S(%), D-Dimer(mg/L), Homocysteine(micromol/L). EndoPAT® was performed in order to obtain reactive hyperemia index (RHI, n.v. >1.67). Oxygen desaturation index (ODI) during sleep was detected by means of nocturnal transcutaneous saturimetry at the time of blood sampling.

Results: Among 14 ROHHAD patients, one presented cerebral venous thrombosis at 3 years of age. EndoPAT® study performed in 6 patients from the original cohort (2M, 4F) displayed a pathologic RHI level was in 4 of them (66.7%). No significant difference was found in thrombotic risk parameters between ROHHAD patients with or without GHD, central adrenal insufficiency, central hypothyroidism, neural tumor, water/electrolyte defects. A strong negative correlation was found between PT and RHI (r= -0.600) and between fibrinogen and RHI (-0,657). No correlation was found between coagulation parameters and blood sodium levels. A strong negative correlation was found between antithrombin levels and ODI (r= -0.721) while no correlation was found between ODI and the other biochemical parameters. A strong positive correlation was found between von Willebrand’s factor and BMI SDS (r= 0.709) and between protein C and BMI (r= 0.828).

Conclusions: Our preliminary results indicate that endothelial damage (shown by lower RHI) might be related to altered coagulation profile in ROHHAD/ROHHADNET patients. Furthermore, BMI and sleep-related respiratory disorders are to be considered as risk factors for thrombotic disorders in these patients. We suggest that thrombotic risk and endothelial damage should undergo careful evaluation in this rare, life-threatening condition.