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Higher plasma orexin a levels in children with Prader-Willi syndrome compared with healthy unrelated sibling controls
Ann M Manzardo1, Lisa Johnson1, Jennifer L Miller2
1Departments of Psychiatry and Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, Kansas.
Insights
Children with Prader-Willi syndrome (PWS) have higher levels of the neuropeptide orexin A. This finding suggests orexin A dysregulation may contribute to PWS-related hyperphagia and behavioral issues.
Area of Science:
- Neuroendocrinology
- Genetics
- Pediatrics
Background:
- Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by hyperphagia, obesity, and behavioral challenges.
- Orexin A, a hypothalamic neuropeptide, regulates feeding behavior and energy metabolism.
- Dysregulation of orexin signaling is hypothesized to contribute to PWS symptoms.
Purpose of the Study:
- To investigate plasma orexin A levels in children with genetically confirmed Prader-Willi syndrome compared to healthy siblings.
- To explore the relationship between orexin A levels and clinical factors in PWS.
Main Methods:
- Plasma orexin A levels were measured in 23 children with PWS and 18 healthy siblings using multiplex immune assays (Milliplex, Luminex platform).
- Data were analyzed using a general linear model, adjusting for diagnosis, gender, age, body fat, and BMI.
- Orexin A levels were natural log-transformed for analysis.
Main Results:
- Children with PWS exhibited significantly higher fasting plasma orexin A levels compared to their healthy siblings (P < 0.006).
- Orexin A levels showed a correlation with age in females with PWS.
- Elevated orexin A levels in PWS remained significant after controlling for covariates.
Conclusions:
- Findings support the hypothesis that orexin A signaling dysregulation is implicated in the hyperphagia and behavioral problems observed in Prader-Willi syndrome.
- Further research is needed to elucidate the complex role of orexin A in PWS pathophysiology.
- This study highlights a potential neurobiological link contributing to core PWS features.
Abstract:
Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder associated with maladaptive social behavior, hyperphagia and morbid obesity. Orexin A is a hypothalamic neuropeptide important as a homeostatic regulator of feeding behavior and in energy metabolism through actions in the lateral hypothalamus. Dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia seen in PWS and we sought to assess orexin A levels in PWS relative to controls children. Morning fasting plasma orexin A levels were analyzed in 23 children (aged 5-11 years) with genetically confirmed PWS and 18 age and gender matched healthy unrelated siblings without PWS. Multiplex immune assays utilized the Milliplex Human Neuropeptide Magnetic panel and the Luminex platform. Natural log-transformed orexin A data were analyzed using general linear model adjusting for diagnosis, gender, age, total body fat, and body mass index (BMI). Plasma orexin A levels were significantly higher (P < 0.006) in children with PWS (average ±SD = 1,028 pg/ml ± 358) compared with unrelated siblings (average ±SD = 609 pg/ml ± 351; P < 0.001). Orexin A levels correlated with age in females and were significantly elevated in PWS even after these effects were controlled. These findings support the hypothesis that dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia in PWS. Further studies are warranted to better understand the complex relationship between orexin A levels and the problematic behaviors consistently found in individuals with PWS. © 2016 Wiley Periodicals, Inc.
