Supplementary appendix

Transcription

1 Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: van Spronsen FJ, van Wegberg AMJ, Ahring K, et al. Key European guidelines for the diagnosis and management of patients with phenylketonuria. Lancet Diabetes Endocrinol 2017; published online Jan 9. S (16)

2 State ment nr Key question Search terms Number of included first second round 1 round 2 Number of final inclusion (critical appraisal 3 ) Level of evidence 1 How should different phenotypes of PKU patients be classified? phenylalanine hydroxylase deficiency, classification, phenotype, phenylalanine loading test, protein loading test, phenylalanine tolerance 71 6 Blaskovics 1974, Blau 2011, ampistol 2011, Guttler 1980, Guttler&Guldberg 1996, van Spronsen Blaskovics 1974 (level 3), Blau 2011 (level 4), ampistol 2011 (level 4), Guttler 1980 (level 4), Guttler&Guldberg 1996 (level 4), van Spronsen 2009 (level 2-) V (Good clinical practice points) Lack of evidence to support statement, Papers are included for background information on several manners of classification 2 Should tetrahydrobiopterin (BH4) deficiencies be excluded by the determination of blood or urinary pterins and DHPR activity in the differential diagnosis of hyperphenylalaninemia? tetrahydrobiopterin deficiency, BH4 deficiency, diagnosis, differential diagnosis, newborn screening, pterin, dihydropteridine reductase, DHPR, loading test Blau 1995, Bonafé 2001, Blau 2011, ao 2014, Dhondt 1991, Ferre 2014, Niederwieser 1985, Opladen 2011, Opladen 2012, Simaite 2014, Trujillano 2014 Blau 1995 (level 3), Bonafé 2001 (level 3), ao 2014 (level /), Dhondt 1991 (level 3), Ferre 2014 (level 3), Niederwieser 1985 (level 3), Opladen 2011 (level/ ), Opladen 2012 (level 3), Simaite 2014 (level 3), Trujillano 2014 (level /) Notwithstanding that most included are of descriptive nature the level of evidence is chosen to be because of the high number of data 3 When should treatment be initiated? Should mild hyperphenylalaninemia be treated? Mild mild HPA, MHP, Non PKU untreated, treatment, diet, initiation, start Berlin 1995, Berry 1979, Blau 20, Boneh 2006, ampistol 2011, ostello 1994, Diamond 1997, Gassio 2005, Gonzalez 2011, Guttler 1980, Hanley 2011, Lang 1989, Levy 1971, Scriver 1995, Smith 1990, Smith 2000, van Spronsen 2011, Weglage 1996a, Weglage 1996b, Weglage 1997, Weglage Berlin 1995 (level 3), Blau 20 (level 4), ampistol 2011 (level 4), ostello 1994 (level 2-/2), Diamond 1997 (level 2), Gassio 2005 (level 2-/2), Smith 1990 (level 2-/2), van Spronsen 2011 (level 4), Weglage 2001 (level 2/2). / D

3 4 Do adult PKU patients need a long term follow-up? Adult, phenylketonuria, PKU, Phenylalanine, Phe levels, Phenylalanine levels, follow up, quality of life, QoL 118 (Phe levels), 51 (follow up), 16 (QoL) Results of searches on bone density, IQ, EF and nutrition were 15 Anwar 2013, Bilder 2013 Daelman 2014, Demirdas 2015, Enns 20, Gokmen 2014, Macdonald 2015, Perez 2005, Pietz 1997, Robertson 2013, Rohde 2014, Rubin 2013, Seki 2015, Trefz 2011, van Spronsen Anwar 2013 (level 3), Daelman 2014 (level 3), Demirdas 2015 (level 1/1), Enns 20 (level 1- /4), Gokmen 2014 (level 2-), Macdonald 2015 (level 3), Perez 2005 (level 2-), Robertson 2013 (level 2-), Rohde 2014 (level 2-), Rubin 2013 (level 3), van Spronsen 2011 (level 4), Trefz 2011 (level 4) 5 6 Which blood Phe-levels or ranges of blood Phe-levels, at which ages, should be aimed for to obtain normal range IQ- and EF-scores in PKU patients until 18 years? Phenylketonuria, PKU, phenylalanine, intelligent quotient, IQ, executive function 55 (EF) 158 (IQ) 42 Albrecht 2009, Anderson 2007, Antshel 2003, Arnold 1998, Berry 2013, Banerjee 2011, Bone 2012, Burgard 1997, Burgard 2000, ampistol 2011, appelletti 2013, de Roche 2008, Diamond 1997, Gassio 2005, Griffiths 2000, Feillet 20, Feldmann 2005, Fonnesbeck 2013, Huijbregts Albrecht 2009 (level 1/1), Diamond 1997 (level 2), Huijbregts 2002a (level 2), Jahja 2014 (level 2), Leuzzi 2004 (level 2), Fonnesbeck 2013 (level 1/1), Moyle 2007 (level 1-/1), Schmidt 1996 (level 2-/2), Waisbren 2007 (level 1), Weglage Statement 5: B

4 2002a, Huijbregts 2002b, Huijbregts 2002c, Huijbregts 2003, Lindegren 2012, Luciana 2001, Jahja 2014, Janos 2012, Leuzzi 2004, McPheeters 2012, Moyle 2007, Sharman 20, Schmidt 1996, Smith 2000, Stemerdink 1994, Trefz 2011, Viau 2011, Waisbren 2000, Waisbren 2007, Weglage 2001, Weglage 2013,Welsh 1990, White 2001, White (level 2) Statement 6: D Indirect evidence 6 What should be optimal target Phe levels in adults? Adult, phenylketonuria, PKU, phenylalanine, Phe level, phenylalanine level 118 Results of searches on Oxidative stress, MRI IQ and EF were also checked for 9 5 from MRI Fonnesbeck 2013, Hoeksma 2009, Koch 2002, Schmidt 1996, Sanayama 2011, TenHoedt 2011, Macleod 2009, Okano 2013, Walter Bick 1993, Kono 2005, Lou 1992, Manara 2009, Weglage Bick 1993 (level 2-), Hoeksma 2009 (level 2-), Kono 2005 (level 2- ), Lou 1992 (level 2-), Manara 2009 (level 2), Sanayama 2011 (level 2-), Schmidt 1996 (level 2- /2), TenHoedt 2011 (level 1), Weglage 2001 (level 2-/2) D Indirect evidence 7 What should be optimal target Phe levels in treated PKU pregnancies to prevent the risk of Maternal PKU syndrome? Maternal, pregnancy, therapy, treatment, therapeutics, phenylalanine level 41 Results of other searches for MPKU were Koch 2000a, Koch 2000b, Koch 2003, LenkeLevy1980, Maillot 2008, Rouse 2000, Rouse 2004, Waisbren 2000, Waisbren 2003, Widaman Koch 2003 (level 2), LenkeLevy1980 (level 2/3), Maillot 2008 (level 2-/2), Rouse 2000 (level 2), Rouse 2004 (level 2/2), Waisbren 2003 (level 2/2), Widaman 2003 (level 2) B 8 Which women with untreated HPA do not need the treatment to prevent the risk of Maternal Hyperphenylalaninemia, pregnancy, maternal, mild, untreated 24 Results of other searches for 8 Koch 2003, Levy 1994, Levy 2003, Matalon 1994, Platt 2000, 4 Levy 1994 (level 2-/2), Levy 2003 (level 2/2), Platt 2000 B

5 PKU syndrome? MPKU were Waisbren 1999, Waisbren 2000, Waisbren 2003 (level 2), Waisbren 2003 (level 2/2) 9 Which micronutrients are at risk of deficiency and need to be monitored in patients with PKU? vitamin, mineral, micronutrient, trace element Arnold 2001, Artuch 2004, Barretto 2008, Bodley 1993, Bohles 1991, olome 2003a, olome 2003b, da ruz 1993, Dobbelaere 2003, Evans 2014, Gassio 2008, Fisberg 1999, Lammardo 2013, Lee 1999, Hanley 1993, Hanley 1996, Huemer 2008, Hvas 2006, Lipinska 1994, Mikoluc 2012, Prochazkova 2013, Robert 2013, Robinson 2000, Schulpis 2002, Schulpis 2003, Schulpis 20, Sierra 1998, Stolen 2014, Vugteveen 2011, Wiig Arnold 2001 (level 3), Barretto 2008 (level 2-), Bodley 1993 (level 2-/3), da ruz 1993 (level 2-/3), Evans 2014 (level 2-/3), Hanley 1993 (level 3), Lammardo 2013 (level 4), Lee 1999 (level 3), Prochazkova 2013 (level 2-), Robert 2013 (level 4), Stolen 2014 (level 2-/3), Vugteveen 2011 (level 2-/3), Wiig 2013 (level 2-/3) What should be done when target levels are out of range, and when should this be initiated? No literature search / / / V (Good clinical practice points) 1 Including included by checking reference lists 2 Including included additionally to first literature selection (e.g. publication date after initial search date or checking reference lists) 3 In cases where reviewers assessed the paper the same, one level of evidence is reported (e.g. 2). In case where reviewers assessed the paper differently, two levels of evidence are reported (eg. 2-/2).