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Objective: To investigate the role of desert hedgehog (Dhh) in a neurodevelopmental disorder known as autism. Subjects and Methods: This study was conducted at the Autism Research and Treatment Center, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia from October 2011 to May 2012. The serum levels of the Dhh protein in 57 patients recently diagnosed with autism and 37 age-matched healthy children were measured using ELISA. The Childhood Autism Rating Scale (CARS) was used for the assessment of autistic severity. Results: The mean serum level of Dhh in patients with autism (1.38 +/- 0.50 ng/ml) was significantly lower (p = 0.0003) than that of normal controls (1.73 +/- 0.37 ng/ml). There was no significant relationship between the serum level of Dhh and the CARS score (p = 0.28), age (p = 0.51) or gender (p = 0.76). Conclusions: The Dhh serum level of patients with autism was lower than that of controls, probably indicating that the serum level of Dhh might be implicated in the physiology of autism. However, this finding should be treated with caution until further investigations are performed with larger populations. (C) 2013 S. Karger AG, Basel