Format

Send to

Choose Destination
Orphanet J Rare Dis. 2015 Mar 28;10:38. doi: 10.1186/s13023-015-0248-3.

Defects in fatty acid amide hydrolase 2 in a male with neurologic and psychiatric symptoms.

Author information

1
Departments of Medicine, University of British Columbia, Vancouver, Canada. Sandra.Sirrs@vch.ca.
2
Departments of Pediatrics, University of British Columbia, Vancouver, Canada. cvankarnebeek@cw.bc.ca.
3
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, Canada. cvankarnebeek@cw.bc.ca.
4
Treatable Intellectual Disability Endeavour in British Columbia (TIDE-BC), Vancouver, Canada. cvankarnebeek@cw.bc.ca.
5
Division of Biochemical Diseases, Rm K3-201, Department of Pediatrics, B.C. Children's Hospital, Centre for Molecular Medicine & Therapeutics, University of British Columbia, 4480 Oak Street, Vancouver, B.C. V6H 3V4, Canada. cvankarnebeek@cw.bc.ca.
6
Department of Anesthesiology, Stony Brook University, Stony Brook, NY, 11794-8480, USA. xiaoxue.peng@stonybrook.edu.
7
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, Canada. casper@cmmt.ubc.ca.
8
Treatable Intellectual Disability Endeavour in British Columbia (TIDE-BC), Vancouver, Canada. casper@cmmt.ubc.ca.
9
Department of Medical Genetics, University of British Columbia, Vancouver, Canada. casper@cmmt.ubc.ca.
10
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, Canada. maja@cmmt.ubc.ca.
11
Treatable Intellectual Disability Endeavour in British Columbia (TIDE-BC), Vancouver, Canada. maja@cmmt.ubc.ca.
12
Department of Medical Genetics, University of British Columbia, Vancouver, Canada. maja@cmmt.ubc.ca.
13
Departments of Biological and Computing Sciences, University of Alberta, Edmonton, T6G 2E8, Canada. rmandal@ualberta.ca.
14
Half Hollow Hills High School, Dix Hills, NY, 11746, USA. dtesta9@optonline.net.
15
Half Hollow Hills High School, Dix Hills, NY, 11746, USA. devindubin@gmail.com.
16
Graduate Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, NY, 11794, USA. gregory.carbonetti@stonybrook.edu.
17
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, 11794-5215, USA. steven.glynn@stonybrook.edu.
18
Departments of Pediatrics, University of British Columbia, Vancouver, Canada. bryan.sayson@cw.bc.ca.
19
Treatable Intellectual Disability Endeavour in British Columbia (TIDE-BC), Vancouver, Canada. bryan.sayson@cw.bc.ca.
20
Department of Medical Genetics, University of British Columbia, Vancouver, Canada. wrobinson@cfri.ca.
21
Departments of Biological and Computing Sciences, University of Alberta, Edmonton, T6G 2E8, Canada. beomsoo@ualberta.ca.
22
Departments of Biological and Computing Sciences, University of Alberta, Edmonton, T6G 2E8, Canada. dwishart@ualberta.ca.
23
Departments of Pediatrics, University of British Columbia, Vancouver, Canada. Colinross1@gmail.com.
24
Treatable Intellectual Disability Endeavour in British Columbia (TIDE-BC), Vancouver, Canada. Colinross1@gmail.com.
25
Department of Medical Genetics, University of British Columbia, Vancouver, Canada. Colinross1@gmail.com.
26
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, Canada. wyeth@cmmt.ubc.ca.
27
Treatable Intellectual Disability Endeavour in British Columbia (TIDE-BC), Vancouver, Canada. wyeth@cmmt.ubc.ca.
28
Department of Medical Genetics, University of British Columbia, Vancouver, Canada. wyeth@cmmt.ubc.ca.
29
Psychiatry, University of British Columbia, Vancouver, Canada. t.hurwitz@ubc.ca.
30
Treatable Intellectual Disability Endeavour in British Columbia (TIDE-BC), Vancouver, Canada. gsinclair@cw.bc.ca.
31
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada. gsinclair@cw.bc.ca.
32
Department of Anesthesiology, Stony Brook University, Stony Brook, NY, 11794-8480, USA. martin.kaczocha@stonybrook.edu.
33
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, 11794-5215, USA. martin.kaczocha@stonybrook.edu.

Abstract

BACKGROUND:

Fatty 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 RESULTS:

Whole 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.

CONCLUSIONS:

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

PMID:
25885783
PMCID:
PMC4423390
DOI:
10.1186/s13023-015-0248-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center