title: Catecholamines in patients with 22q11.2 deletion syndrome and the low-activity COMT polymorphism.
abstract: OBJECTIVE
  To investigate catecholamine phenotypes and the effects of a tyrosine hydroxylase inhibitor in individuals with the 22q11.2 deletion syndrome and low-activity catechol-O-methyltransferase (COMT).
  
  
  BACKGROUND
  Many persons with the 22q11.2 deletion syndrome suffer severe disability from a characteristic ultrarapid-cycling bipolar disorder and associated "affective storms." One etiologic hypothesis for this condition is that deletion of the COMT gene from one chromosome 22 results in increased catecholamine neurotransmission, particularly if the undeleted chromosome 22 encodes a variant of COMT with low activity.
  
  
  METHODS
  In a preliminary study, plasma, urine, and CSF catecholamines and catecholamine metabolites were measured in four teenage patients with a neuropsychiatric condition associated with 22q11.2 deletion and the low-activity COMT polymorphism on the nondeleted chromosome. In these four patients, and an additional institutionalized adult with the condition, an uncontrolled, open-label trial of metyrosine was administered in an attempt to lower catecholamine production and to alleviate symptoms.
  
  
  RESULTS
  Mild elevations of baseline CSF homovanillic acid (HVA) were found in three of four patients and a moderate reduction in CSF HVA after metyrosine treatment in the patient with the highest pretreatment concentration. The course of the five patients during the clinical trial is described.
  
  
  CONCLUSIONS
  In patients with the 22q11.2 deletion syndrome and low-activity COMT, controlled studies of pharmacologic agents that decrease catecholamine production, block presynaptic catecholamine storage, or enhance S-adenosylmethionine, the cosubstrate of COMT, are warranted.
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, USA wgraf@accordfoundation.org.
authors.forename: W D
authors.initials: WD
authors.lastname: Graf
authors.forename: A S
authors.initials: AS
authors.lastname: Unis
authors.forename: C M
authors.initials: CM
authors.lastname: Yates
authors.forename: S
authors.initials: S
authors.lastname: Sulzbacher
authors.forename: M B
authors.initials: MB
authors.lastname: Dinulos
authors.forename: R M
authors.initials: RM
authors.lastname: Jack
authors.forename: K A
authors.initials: KA
authors.lastname: Dugaw
authors.forename: M N
authors.initials: MN
authors.lastname: Paddock
authors.forename: W W
authors.initials: WW
authors.lastname: Parson
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002395:Catecholamines / Q000378:metabolism*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D013577:Syndrome
chemical_list: D002395:Catecholamines; D002394:Catechol O-Methyltransferase