Birth prevalence of phenylalanine hydroxylase deficiency: a systematic literature review and meta-analysis

Foreman, Pamela K.; Margulis, Andrea V.; Alexander, Kimberly; Shediac, Renee; Calingaert, Brian; Harding, Abenah; Pladevall-Vila, Manel; Landis, Sarah

doi:10.1186/s13023-021-01874-6

Orphanet Journal of Rare Diseases

Table 3 Birth prevalence estimates scoring strong on diagnostic method for case confirmation (n = 54 publications)

From: Birth prevalence of phenylalanine hydroxylase deficiency: a systematic literature review and meta-analysis

Country	Birth prevalence per 10,000 newborns (95% CI)	Phe cutoff value for confirmatory diagnosis (µmol/L)	Score for additional quality of evidence domains^e				References
Country	Birth prevalence per 10,000 newborns (95% CI)	Phe cutoff value for confirmatory diagnosis (µmol/L)	Case definition	Study setting source population	Statistical methods	Precision of prevalence estimate	References
Europe
Austria (Eastern, PKU^f)	1.3 (0.92–1.83)^d	NR	Weak	Strong	Strong	Strong	Thalhammer [49]
Austria (Eastern, HPA^f)	0.49 (0.28–0.85)^d	NR	Weak	Strong	Strong	Moderate	Thalhammer [49]
Austria (Western, PKU^f)	0.45 (0.23–0.88)^d	NR	Weak	Strong	Strong	Moderate	Thalhammer [49]
Austria (Western, HPA^f)	0.5 (0.26–0.96)^d	NR	Weak	Strong	Strong	Moderate	Thalhammer [49]
Estonia	0 (0–1.02)^d	< 600	Strong	Strong	Strong	Weak	Ounap et al. [38]
Estonia	1.66 (0.76–3.63)^c,d	1000	Strong	Strong	Strong	Moderate	Ounap et al. [38]
Finland	0 (0–0.52)^a,d	363	Moderate	Strong	Strong	Weak	Visakorpi et al. [39]
Germany	0.81 (0.66–1)^d	NR	Weak	Strong	Strong	Strong	Lindner et al. [50]
Germany	0.78 (0.63–0.97)^b,d	600	Moderate	Strong	Strong	Strong	Lindner et al. [50]
Germany	0.81 (0.65–1.01)^a,d	363– < 908	Strong	Strong	Strong	Strong	Mathias and Bickel [51]
Germany	0.99 (0.81–1.21)^a,d	908	Strong	Strong	Strong	Strong	Mathias and Bickel [51]
Germany	0.96 (0.65–1.43)	600	Strong	Strong	Strong	Strong	Schulze et al. [52]
Germany	1.24 (0.87–1.76)	150–600	Strong	Strong	Strong	Strong	Schulze et al. [52]
Greece	0.44 (0.05–1.61)^d	NR	Moderate	Moderate	Strong	Weak	Loukas et al. [53]
Greece	0.41 (0.31–0.56)^c,d	1211	Strong	Strong	Strong	Strong	Missiou-Tsagaraki et al. (1988) [54]
Hungary	0.85 (0.39–1.86)^d	NR	Weak	Strong	Strong	Moderate	Mehes et al. [55]
Italy (PKU^f)	1.38 (0.85–2.23)^d	NR	Moderate	Weak	Strong	Moderate	Antonozzi et al. [56]
Italy (HPA^f)	0.26 (0.05–0.75)^d	NR	Moderate	Weak	Strong	Weak	Antonozzi et al. [56]
Italy	0.22 (0.15–0.32)^c,d	1211	Strong	Strong	Strong	Strong	Zaffanello et al. [57]
Italy	0.78 (0.63–0.96)^d	NR	Moderate	Strong	Strong	Strong	Zaffanello et al. [57]
Macedonia	2.46 (0.06–13.68)^d	151	Moderate	Strong	Strong	Weak	Kocova and Anastasovska [41]
Poland	0.28 (0.22–0.34)^a,d	363–1211	Strong	Moderate	Strong	Strong	Cabalska et al. [58]
Poland	1.29 (1.16–1.42)^a,c,d	1211	Strong	Moderate	Strong	Strong	Cabalska et al. [58]
Portugal	0.82 (0.56–1.2)^a,d	360	Strong	Strong	Strong	Strong	Vilarinho et al. [59]
Portugal	0.38 (0.22–0.66)^d	150–360	Strong	Strong	Strong	Moderate	Vilarinho et al. [59]
Slovakia	1.69 (1.45–1.98)^d	NR	Weak	Strong	Strong	Strong	Dluholucký et al. [60]
Slovenia	0.98 (0.72–1.35)^b,c,d	1200	Strong	Strong	Moderate	Strong	Smon et al. [61]
Slovenia	0.39 (0.24–0.64)^b,d	600–900	Strong	Strong	Moderate	Moderate	Smon et al. [61]
Slovenia	0.1 (0.03–0.27)^b,d	900–1200	Strong	Strong	Moderate	Weak	Smon et al. [61]
Spain	0.66 (0.22–1.55)^d	240	Strong	Strong	Strong	Weak	Fernández-Iglesias et al. [62]
USSR/Russia	1.5 (0.98–2.3)^b,c,d	1200	Moderate	Strong	Strong	Strong	Gerasimova et al. [63]
USSR/Russia	0.36 (0.12–0.84)^b,d	600–1200	Moderate	Strong	Strong	Weak	Gerasimova et al. [63]
United Kingdom	0.49 (0.36–0.67)^c,d	1200	Strong	Moderate	Strong	Strong	Walker et al. [64]
United Kingdom	0.19 (0.11–0.31)^d	240	Strong	Moderate	Strong	Moderate	Walker et al. [64]
Yugoslavia	0.22 (0.1–0.48)^b,d	605–902	Strong	Moderate	Strong	Moderate	Mardesic et al. [65]
Yugoslavia	0.69 (0.44–1.08)^b,d	908	Strong	Moderate	Strong	Strong	Mardesic et al. [65]
Latin America
Brazil (Laboratory A, 2005)	0.36 (0.12–0.84)^b,d	605	Strong	Strong	Strong	Weak	Botler et al. [66]
Brazil (Laboratory A, 2006)	0.59 (0.31–1.12)^b,d	605	Strong	Strong	Strong	Intermediate	Botler et al. [66]
Brazil (Laboratory A, 2007)	0.35 (0.11–0.82)^b,d	605	Strong	Strong	Strong	Weak	Botler et al. [66]
Brazil (Laboratory B, 2005)	0.52 (0.06–1.9)^b,d	605	Strong	Strong	Strong	Weak	Botler et al. [66]
Brazil (Laboratory B, 2006)	0.84 (0.17–2.45)^b,d	605	Strong	Strong	Strong	Weak	Botler et al. [66]
Brazil (Laboratory B, 2007)	0.91 (0.11–3.28)^b,d	605	Strong	Strong	Strong	Weak	Botler et al. [66]
Brazil	0.92 (0.25–2.36)^a–d	1211	Strong	Strong	Strong	Weak	Ramalho et al. [67]
Brazil	0.23 (0.01–1.28)^a,d	302–604	Strong	Strong	Strong	Weak	Ramalho et al. [67]
Brazil	0.23 (0.01–1.28)^a,b,d	606–1210	Strong	Strong	Strong	Weak	Ramalho et al. [67]
Chile	0.53 (0.45–0.63)^c,d	1211	Strong	Strong	Strong	Strong	Cornejo et al. [68]
Chile	0.98 (0.86–1.11)^d	NR	Intermediate	Strong	Strong	Strong	Cornejo et al. [68]
Middle East/North Africa
Iran	0.15 (0.07–0.32)^b,c,d	1211	Strong	Strong	Strong	Intermediate	Abbaskhanian et al. [69]
Iran	0.29 (0.17–0.52)^d	121–605	Strong	Strong	Strong	Intermediate	Abbaskhanian et al. [69]
Iran	0.22 (0.12–0.42)^b,d	606–1210	Strong	Strong	Strong	Intermediate	Abbaskhanian et al. [69]
Iran	1.6 (1.11–2.31)^a,d	424	Strong	Strong	Strong	Strong	Habib et al. [44]
Iran	0.52 (0.14–1.33)^d	121– < 1211	Strong	Strong	Strong	Weak	Karamifar et al. [70]
Iran	0.39 (0.08–1.14)^c,d	1211	Strong	Strong	Strong	Weak	Karamifar et al. [70]
Iran	1.92 (1.53–2.41)^d	NR	Intermediate	Strong	Intermediate	Strong	Motamedi et al. [71]
Saudi Arabia	0.68 (0.52–0.89)^d	180	Strong	Strong	Strong	Strong	Alfadhel et al. [72]
Turkey (classical PKU^f)	1.35 (1.18–1.54)^d	NR	Weak	Strong	Strong	Strong	Ozalp et al. [73]
Turkey (mild PKU^f)	0.64 (0.52–0.77)^d	NR	Weak	Strong	Strong	Strong	Ozalp et al. [73]
Turkey (mild HPA^f)	0.36 (0.28–0.47)^d	NR	Weak	Strong	Strong	Strong	Ozalp et al. [73]
UAE	0.76 (0.57–0.99)^c,d	1211	Strong	Strong	Strong	Strong	Al Hosani et al. [74]
North America
Canada (Alberta)	0.50 (CI not estimable)	NR	Weak	Intermediate	Strong	Weak	Somers and Favreau [37]
Canada (Ontario, PKU^f)	0.60 (CI not estimable)	NR	Weak	Intermediate	Strong	Weak	Somers and Favreau [37]
Canada (Ontario, HPA^f)	0.29 (CI not estimable)	NR	Weak	Intermediate	Strong	Weak	Somers and Favreau [37]
US (NC)	0.08 (0.01–0.3)	157	Intermediate	Strong	Strong	Weak	Frazier et al. [42]
US (NC)	0.46 (0.26–0.82)	250	Intermediate	Strong	Strong	Intermediate	Frazier et al. [42]
US (NC)	0.52 (0.39–0.69)^a,d	300	Intermediate	Strong	Strong	Strong	Frazier et al. [42]
US (NY)	0.1 (0.05–0.2)^d	908– < 1211	Strong	Strong	Intermediate	Intermediate	Hansen et al. [75]
US (NY)	0.53 (0.39–0.72)^c,d	1211	Strong	Strong	Intermediate	Strong	Hansen et al. [75]
US (NY)	0.14 (0.07–0.25)^d	NR	Intermediate	Strong	Intermediate	Intermediate	Hansen et al. [75]
US (NY)	0.7 (0.52–0.93)^d	NR	Intermediate	Strong	Intermediate	Strong	Kelly and Palombi [76]
US (MA)	1.04 (0.62–1.75)^d	NR	Intermediate	Strong	Strong	Intermediate	Maccready and Hussey [28]
US (CT)	0.83 (CI not estimable)	NR	Weak	Intermediate	Strong	Weak	Somers and Favreau [37]
US (FL)	1.00 (CI not estimable)	NR	Weak	Intermediate	Strong	Weak	Somers and Favreau [37]
US (KS)	0.80 (CI not estimable)	NR	Weak	Intermediate	Strong	Weak	Somers and Favreau [37]
US (KY)	0.87 (CI not estimable)	NR	Weak	Intermediate	Strong	Weak	Somers and Favreau [37]
US (OK)	0.59 (CI not estimable)	NR	Weak	Intermediate	Strong	Weak	Somers and Favreau [37]
US (PA, PKU^f)	0.78 (CI not estimable)	NR	Weak	Intermediate	Strong	Weak	Somers and Favreau [37]
US (PA, HPA^f)	0.18 (CI not estimable)	NR	Weak	Intermediate	Strong	Weak	Somers and Favreau [37]
US (TX)	0.38 (CI not estimable)	NR	Weak	Intermediate	Strong	Weak	Somers and Favreau [37]
US (VA)	0.57 (CI not estimable)	NR	Weak	Intermediate	Strong	Weak	Somers and Favreau [37]
US (WV)	0.67 (CI not estimable)	NR	Weak	Intermediate	Strong	Weak	Somers and Favreau [37]
US (PA)	0.43 (0.29–0.64)^a,d	363	Strong	Strong	Strong	Strong	Wainer and Sideman [43]
US (PA)	0.9 (0.68–1.19)^d	NR	Intermediate	Strong	Strong	Strong	Wainer and Sideman [43]
US (New England)	0.27 (0.13–0.56)^d	NR	Intermediate	Strong	Strong	Intermediate	Zytkovicz et al. [77]
US (New England)	0.43 (0.24–0.77)^d	NR	Intermediate	Strong	Strong	Intermediate	Zytkovicz et al. [77]
Southeast Asia
Thailand	0.04 (0.01–0.08)	NR	Intermediate	Strong	Strong	Weak	Charoensiriwatana et al. [78]
Thailand	0.05 (0.02–0.11)	1211	Strong	Strong	Strong	Weak	Pangkanon et al. [79]
Thailand	0.03 (0.02–0.05)^c,d	1200	Intermediate	Strong	Strong	Intermediate	Pangkanon et al. [80]
Thailand	0 (0–2.12)	NR	Intermediate	Intermediate	Strong	Weak	Ratrisawadi et al. [40]
Thailand	0.04 (0.01–0.1)	NR	Intermediate	Strong	Strong	Weak	Sutivijit et al. [81]
West Pacific
Australia	0.26 (0.09–0.61)^d	200–300	Intermediate	Intermediate	Strong	Weak	Boneh et al. [34]
Australia	0.37 (0.18–0.76)^b,d	600–1200	Intermediate	Intermediate	Strong	Intermediate	Boneh et al. [34]
Australia	0.05 (0–0.29)^b,d	2600	Intermediate	Intermediate	Strong	Weak	Boneh et al. [34]
China	0.17 (0.08–0.36)	242–1211	Strong	Strong	Strong	Intermediate	Chen et al. [82]
China	0.59 (0.38–0.89)^c	1211	Strong	Strong	Strong	Strong	Chen et al. [82]
China	0.38 (0.23–0.64)^d	NR	Weak	Strong	Strong	Intermediate	Lin et al. [29]
China	0.1 (0.01–0.36)^a,d	363– < 908	Strong	Strong	Strong	Weak	Liu and Zuo [83]
China	0.5 (0.27–0.93)^a,d	908 or 1211	Strong	Strong	Strong	Intermediate	Liu and Zuo [83]
China	0.4 (0.34–0.47)	NR	Intermediate	Strong	Strong	Strong	Maitusong et al. [84]
China	0.91 (0.65–1.28)	NR	Weak	Intermediate	Strong	Strong	Shi et al. [85]
China	0.65 (0.48–0.9)^a,c,d	1200	Strong	Strong	Weak	Strong	Su et al. [86]
China	0.28 (0.17–0.45)^d	120–360	Strong	Strong	Weak	Intermediate	Su et al. [86]
China	0.98 (0.76–1.27)^a,d	360–1200	Strong	Strong	Weak	Strong	Su et al. [86]
China	0.88 (0.46–1.67)	NR	Weak	Strong	Strong	Intermediate	Tu et al. [87]
China	0.07 (0.01–0.21)^a–d	1200	Strong	Strong	Strong	Weak	Wang et al. [88]
China	0.1 (0.03–0.24)^d	120–360	Strong	Strong	Strong	Weak	Wang et al. [88]
China	0.05 (0.01–0.17)^a,d	360–600	Strong	Strong	Strong	Weak	Wang et al. [88]
China	0.14 (0.07–0.31)^a,b,d	600–1200	Strong	Strong	Strong	Intermediate	Wang et al. [88]
China	0.86 (0.82–0.91)^d	NR	Intermediate	Strong	Strong	Strong	Zhan et al. [89]
South Korea	0.51 (0.14–1.29)^c,d	1200	Strong	Strong	Strong	Weak	Yoon et al. [90]
Taiwan	0.27 (0.2–0.36)^d	120– < 600	Strong	Strong	Strong	Strong	Niu et al. [91]
Taiwan	0.13 (0.09–0.21)^b,d	600– < 1200	Strong	Strong	Strong	Strong	Niu et al. [91]
Taiwan	0.03 (0.01–0.08)^b–d	1200	Strong	Strong	Strong	Weak	Niu et al. [91]

CI = confidence interval; CT = Connecticut; FL = Florida; HPA = hyperphenylalaninemia; KS = Kansas; KY = Kentucky; MA = Massachusetts; NC = North Carolina; NR = not reported; NY = New York; OK = Oklahoma; PA = Pennsylvania; Phe = phenylalanine; PKU = phenylketonuria; TX = Texas; UAE = United Arab Emirates; US = United States; USSR = Union of Soviet Socialist Republics; VA = Virginia; WV = West Virginia
^aEstimate contributes to meta-analysis with diagnostic cutoff value 360 µmol/L
^bEstimate contributes to meta-analysis with diagnostic cutoff value 600 µmol/L
^cEstimate contributes to meta-analysis with diagnostic cutoff value 1200 µmol/L
^dEstimate contributes to overall meta-analysis
^eThis table includes only estimates for which the method of diagnosis confirmation was considered “strong” in the quality of evidence scoring tool
^fNominal diagnoses as provided in associated reference

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ISSN: 1750-1172

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