Online-Only Supplementary Material

Supplementary Table 1. Recommended target blood Phe concentrations (μmol/L) from national or local guidelines from individual European countries

Age (y) / B / D / DK / E / I / N / NL / PL / TR / UK
<1 / 42–240 / 42–240 / 120–300 / <360 / <360 / 120–400 / 120–360 / 120–360 / 120–360 / 100–360
1–3 / 42–240 / 42–240 / 1–3 y: 120–300 / <360 / <360 / 120–400 / 120–360 / 120–360 / 120–360 / 100–360
4–10 / 42–240 / 42–240 / 4–8 y: 120–400
8–10 y:120–600 / <480 / <360 / 120–400 / 120–360 / 120–360 / 120–360 / 100–450
11–16 / 42–600 / 42–900 / 10–12 y:120–700
>12 y: 900 / <630 / <480 / 120–400 / <12 y: 120–360
>12 y: 120–600 / 120–600 / <720 / 100–700
Adult (>16) / 42–900 / 42–1200 / 120–900 / <630 / <600 / 120–400 / 120–600 / 120–720 / <900 / 100–700
On LNAA / N/A / N/A / 120–1500 / N/A / NR / <1500 / N/A / N/A / N/A / N/A

B: Nutrition and Metabolism Unit, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium; D: Dept. of Metabolism and Nutrition, Dr von Hauner Children's Hospital, University of Munich, Munich, Germany; DK: Department of PKU, Kennedy Centre, Glostrup, Denmark; E: Unidad Enfermendades Metabolices Servicio de Pediatria Hospital Ramon y Cajal, Madrid, Spain; I: Dept. of Pediatrics, San Paolo Hospital University of Milan, Milan, Italy; N: Division of Pediatrics and Dept. of Pediatric Research, Oslo University Hospital-Rikshospitalet, Oslo, Norway; NL: Section of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, The Netherlands; PL: Dept. of Pediatrics, National Research Institute of Mother and Child, Warszawa, Poland; TR: Dept. of Nutrition and Dietetics, Hacettepe University İhsan Doğramacı Children’s Hospital, Metabolism Unit, Ankara, Turkey; UK: The Children’s Hospital, Birmingham, UK. NR: no recommendation; N/A: not applicable - large neutral amino acid (LNAA) supplements were not used routinely in these countries.

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SupplementaryTable 2Median (range) blood Pheconcentrations (µmol/L) achieved within 12 months in patients with PKU

Age (y) / B / D / DK / E / I / N / NL / PL / TR1 / UK
<1 / 174
(162-219) / 144
(96-342) / 296
(18-2299) / 66
(6-216) / 135
(90-276) / 313
(215-327) / 175
(175) / 198
(66-288) / 185
(20-974) / 135
(120-155)
1–3 / 234
(60-486) / 168
(102-306) / 222
(10-3140) / 246
(24-402) / 170
(120-330) / 346
(232-487) / 226
(193-389) / 246
(60-1146) / 337
(44-950) / 200
(155-355)
4–10 / 270
(90-960) / 192
(108-438) / 382
(33-1198) / 270
(90-450) / 200
(42-546) / 334
(211-601) / 303
(192-533) / 306
(60-1896) / 553
(108-1661) / 248
(150-565)
11–16 / 408
(174-969) / 468
(276-1050) / 615
(74-1795) / 462
(234-780) / 258
(27-585) / 532
(241-1930) / 327
(167-1077) / 510
(36-1572) / 897
(197-1838) / 250
(190-1190)
Adult (>16) / 828
(120-1380) / 864
(222-1410) / 769
(26-2102) / 588
(330-1038) / 603
(87-1329) / 784
(270-1735) / 581
(234-1261) / 930
(180-2208) / 944
(184-1325) / 608
(80-1220)
On LNAA / N/A / N/A / 1297
(27-2102) / N/A / 876
(159-1338) / 1274
(487-1878) / N/A / N/A / N/A / N/A

Data shown are median (range) blood Phe concentrations (µmol/L) achieved in patients with PKUover a period of 12 months (2007 – 2008) in each centre. N/A: Not applicable - large neutral amino acid (LNAA) supplements were not used routinely in these countries. Country abbreviations are as shown for Supplementary Table 1. 1Based on one month of treatment among patients attending clinics.

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SupplementaryTable 3Median percentages of blood samples with Phe concentrations within or below age-specific recommended Phe levels in patients with PKU

Age(y) / B / D / DK / E / I / N / NL / PL / TR1 / UK
<1 / 87 / 86 / 56 / 100 / 98 / 97 / 81 / 89 / 79 / 93
1–3 / 67 / 78 / 67 / 87 / 100 / 69 / 84 / 67 / 0 / 94
4–10 / 33 / 73 / 83 / 100 / 100 / 68 / 75 / 54 / 25 / 85
11–16 / 94 / 100 / 87 / 91 / 100 / 15 / 84 / 57 / 0 / 95
Adult
(>16) / 76 / 100 / 42 / 90 / 89 / 0 / 54 / 23 / 50 / 86
On LNAA / N/A / N/A / 72 / N/A / NR / 100 / N/A / N/A / N/A / N/A

Data shown are median percentages of blood samples from patients in each centre that met guideline criteria for Phe concentrations. Country abbreviations are as shown for Supplementary Table 1. 1Based on one month of treatment among patients attending clinics.

SupplementaryTable 4Median percentages of blood Phe samples returned according to national/local guidelines in each country

Age (y) / B / D / DK / E / I / N / NL / PL / UK
<1 / 59 / 104 / 129 / 111 / 84 / 102 / 131 / 102 / 112
1–3 / 63 / 102 / 92 / 208 / 120 / 173 / 121 / 63 / 99
4–10 / 117 / 92 / 86 / 162 / 92 / 112 / 154 / 67 / 90
11–16 / 50 / 83 / 66 / 100 / 83 / 69 / 92 / 50 / 87
Adult
(>16) / 42 / 75 / 51 / 75 / 54 / 55 / 63 / 33 / 75
On LNAA / N/A / N/A / 35 / N/A / 3 / 27 / N/A / N/A / N/A

Data shown are medians based on the numbers of blood Phe samples returned by each patient expressed as a percentage of the number of samples required by guidelines. Data from Turkey are not shown as this centre does not employ a home blood sampling system (blood tests are carried out when patients attend the clinic); N/A: not applicable - large neutral amino acid (LNAA) supplements were not used routinely in these countries. Country abbreviations are as shown for Supplementary Table 1.

Supplementary Table 5 Number of patients with PKU on dietary management included in the analysis

B / D / DK / E / I / N / NL / PL / TR1 / UK / Total
a) Subjects included in the analysis
Age (y)
<1 /
4 /
5 /
12 /
6 /
6 /
5 /
1 /
16 /
20 /
6 /
81
1–3 / 15 / 17 / 19 / 12 / 14 / 9 / 10 / 42 / 68 / 11 / 217
4–10 / 28 / 23 / 71 / 14 / 70 / 26 / 20 / 127 / 77 / 30 / 486
11–16 / 9 / 25 / 45 / 23 / 43 / 34 / 15 / 113 / 29 / 26 / 362
Adult (>16) / 40 / 39 / 72 / 46 / 89 / 83 / 36 / 175 / 10 / 40 / 660
On LNAA / – / – / 89 / – / 20 / 6 / – / – / – / – / 115
Total2 / 96 / 109 / 308 / 101 / 242 / 163 / 82 / 473 / 204 / 113 / 1921
b) Selected reasons for exclusion from the analysis
Adult3 not on diet / 1 / 17 / 18 / 35 / 3 / 15 / 3 / 61 / 1 / 34 / 188
Pregnant/pre-conception diet / 3 / 3 / 8 / 3 / 0 / 8 / 3 / 9 / 1 / 2 / 40
Other4 / 9 / 51 / 12 / 11 / 0 / 30 / 5 / 4 / NA / 21 / 143

All patients were managed using a Phe-restricted diet. 1based on one month of treatment. 2Total study population. 3Age >16 y. NA: because these values are based on one month’s clinic attendance only for patients in the Turkish centre, these data are not available. 4Lost to follow up, no blood samples received in the period of study from all age groups. B: Nutrition and Metabolism Unit, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium; D: Dept. of Metabolism and Nutrition, Dr. von Hauner Children's Hospital, University of Munich, Munich, Germany; DK: Department of PKU, Kennedy Centre, Glostrup, Denmark; E: Unidad Enfermendades Metabolices Servicio de Pediatria Hospital Ramon y Cajal, Madrid, Spain; I: Dept. of Pediatrics, San Paolo Hospital University of Milan, Milan, Italy; N: Division of Pediatrics and Dept. of Pediatric Research, Oslo University Hospital-Rikshospitalet, Oslo, Norway; NL: Section of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, The Netherlands; PL: Dept. of Pediatrics, National Research Institute of Mother and Child, Warszawa, Poland; TR: Hacettepe University İhsan Doğramacı Children’s Hospital, Metabolism Unit, Ankara, Turkey; UK: The Children’s Hospital, Birmingham, UK.

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