title: A Systematic Review of BH4 (Sapropterin) for the Adjuvant Treatment of Phenylketonuria.
abstract: BACKGROUND
  Dietary management is the mainstay of effective treatment in PKU, but dietary restriction is difficult and additional treatment options are needed.
  
  
  OBJECTIVE
  To systematically review evidence regarding sapropterin (BH4) use as an adjunct to dietary restriction in individuals with PKU.
  
  
  METHODS
  Five databases including MEDLINE up to August 2011.
  
  
  METHODS
  Two reviewers independently assessed studies against predetermined inclusion/exclusion criteria.
  
  
  METHODS
  Two reviewers independently extracted data regarding participant and intervention characteristics and outcomes and assigned overall quality and strength of evidence ratings based on predetermined criteria.
  
  
  RESULTS
  BH4 research includes two randomized controlled trials (RCTs) and three uncontrolled open-label trials. Phenylalanine (Phe) levels were reduced by at least 30 % in up to half of treated participants (32-50 %). In one RCT comparing placebo on likelihood of a 30 % reduction in Phe, 9 % of those on placebo achieved this effect, compared with 44 % of the treated group after 6 weeks. Phe tolerance and variability were improved in treated participants in studies assessing those outcomes. No comparative studies assessed long-term outcomes including cognitive effects, nutritional status, or quality of life.
  
  
  CONCLUSIONS
  Adjuvant pharmacologic therapy has the potential to support individuals in achieving optimal Phe levels. BH4 has been shown to reduce Phe levels in some individuals, with significantly greater reductions seen in treated versus placebo groups. The strength of the evidence is moderate for short-term effects on reducing Phe in a subset of initially BH4-responsive individuals, moderate for a lack of significant harms, low for longer-term effects on cognition, and insufficient for all other outcomes.
authors: Division of General Pediatrics and Vanderbilt Institute for Global Health, Vanderbilt Medical Center, 2200 Children's Way, 8232 Doctors' Office Tower, Nashville, TN, 37232-9225, USA, marylou.lindegren@Vanderbilt.Edu.
authors: Mary Lou
authors: ML
authors: Lindegren
authors: Shanthi
authors: S
authors: Krishnaswami
authors: Tyler
authors: T
authors: Reimschisel
authors: Christopher
authors: C
authors: Fonnesbeck
authors: Nila A
authors: NA
authors: Sathe
authors: Melissa L
authors: ML
authors: McPheeters