Defects in fatty acid amide hydrolase 2 in a male with neurologic and psychiatric symptomsReportar como inadecuado

Defects in fatty acid amide hydrolase 2 in a male with neurologic and psychiatric symptoms - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Orphanet Journal of Rare Diseases

, 10:38

First Online: 28 March 2015Received: 22 January 2015Accepted: 03 March 2015DOI: 10.1186-s13023-015-0248-3

Cite this article as: Sirrs, S., van Karnebeek, C.D., Peng, X. et al. Orphanet J Rare Dis 2015 10: 38. doi:10.1186-s13023-015-0248-3


BackgroundFatty acid amide hydrolase 2 FAAH2 is a hydrolase that mediates the degradation of endocannabinoids in man. Alterations in the endocannabinoid system are associated with a wide variety of neurologic and psychiatric conditions, but the phenotype and biochemical characterization of patients with genetic defects of FAAH2 activity have not previously been described. We report a male with autistic features with an onset before the age of 2 years who subsequently developed additional features including anxiety, pseudoseizures, ataxia, supranuclear gaze palsy, and isolated learning disabilities but was otherwise cognitively intact as an adult.

Methods and resultsWhole exome sequencing identified a rare missense mutation in FAAH2, hg19: g.57475100G > T c.1372G > T resulting in an amino acid change p.Ala458Ser, which was Sanger confirmed as maternally inherited and absent in his healthy brother. Alterations in lipid metabolism with abnormalities of the whole blood acyl carnitine profile were found. Biochemical and molecular modeling studies confirmed that the p.Ala458Ser mutation results in partial inactivation of FAAH2. Studies in patient derived fibroblasts confirmed a defect in FAAH2 activity resulting in altered levels of endocannabinoid metabolites.

ConclusionsWe propose that genetic alterations in FAAH2 activity contribute to neurologic and psychiatric disorders in humans.

KeywordsFatty acid amide hydrolase 2 FAAH1 FAAH2 Anandamide Endocannabinoids Intellectual developmental disability Ataxia Anxiety Psychiatric diseases AbbreviationsECSEndocannabinoid system


FAAHFatty Acid Amide Hydrolase

MAFMinor allele frequency

MADDMultiple acylCoA dehydrogenase deficiency

MRMMultiple reaction monitoring

CADDCombined Annotation Dependent Depletion

WTWild Type

FAOFatty Acid Oxidation

Sandra Sirrs, Clara DM van Karnebeek, and Xiaoxue Peng contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s13023-015-0248-3 contains supplementary material, which is available to authorized users.

Download fulltext PDF

Autor: Sandra Sirrs - Clara DM van Karnebeek - Xiaoxue Peng - Casper Shyr - Maja Tarailo-Graovac - Rupasri Mandal - Daniel Testa


Documentos relacionados