Table 1.
Main characteristics of included studies.
| Reference | Country | Study Design | Study Period | PKU Phenotype | Age Range (Years) | Gender (Male:Female) | Ethnic Origin | Duration of Follow-Up (Years) |
|---|---|---|---|---|---|---|---|---|
| (Sample Size, n) | ||||||||
| Kennedy et al., 1967 [8] | USA | Prospective longitudinal | 1962–1966 | Classical (n = 27) | 0–3 | N/A | N/A | 2 to 3 |
| Mild-moderate (n = 10) | ||||||||
| Atypical (n = 11) | ||||||||
| Total (n = 48) | ||||||||
| Hoeksma et al., 2005 [36] | The Netherlands | Retrospective longitudinal multicentre | 1974–1995 | N/A (Total n = 174) | 0–3 | N/A | Caucasian | 3 |
| Verkerk et al., 1994 [19] | The Netherlands | Prospective longitudinal | 1974–1988 | N/A (Total n = 137) | N/A | N/A | Caucasian | 10 |
| Schaefer et al., 1994 [20] | Germany | Prospective longitudinal | 1978–1984 | N/A (Total n = 82) | 0–6 | 39:43 | Caucasian | 6 |
| Dhondt et al., 1995 [22] | France | Retrospective longitudinal | 1969–1987 | N/A (Total n = 94) | 0–10 | 48:46 | Caucasian | 10 |
| Aldámiz-Echevarría et al., 2014 [31] | Spain | Retrospective, longitudinal, multicentre | N/A | Classical (n = 158) | 1–36 | 236:269 | Caucasian | PKU: 18, |
| Mild-moderate (n = 121) | ||||||||
| Mild HPA (n = 226) | mHPA: 12 | |||||||
| Total (n = 505) | ||||||||
| Thiele et al., 2017 [32] | Germany | Retrospective longitudinal | 1969–2014 | PKU (n = 183) | 0–18 | 119:105 | Caucasian | 18 |
| Mild HPA (n = 41) | ||||||||
| Total (n = 224) | ||||||||
| Belanger-Quintana et al., 2011 [26] | Spain | Retrospective, longitudinal, single centre | 1979–2008 | Classical (n = 34) | 1–28 | 75:85 | N/A | PKU: 18, |
| Mild-moderate (n = 65) | ||||||||
| Mild HPA (n = 61) | mHPA: 9 | |||||||
| Total (n = 160) | ||||||||
| Couce et al., 2015 [27] | Spain | Retrospective longitudinal | 1980–2011 | Classical (n = 30) | N/A | 45:64 | N/A | 18 |
| Mild-moderate (n = 24) | ||||||||
| Mild HPA (n = 55) | ||||||||
| Total (n = 109) | ||||||||
| Evans et al., 2017 [28] | Australia | Prospective longitudinal | 1996–2014 | N/A (Total n = 32) | 0.83–18 | 10:22 | N/A | 2 |
| van der Schot et al., 1994 [37] | The Netherlands | Prospective longitudinal | N/A | Classical PKU (n = 33) | N/A | N/A | N/A | 2 |
| Chang et al., 1984 [38] | USA | Retrospective longitudinal | 1968–1977 | Classical PKU (n = 67) | N/A | 31:36 | N/A | 6 |
| Kindt et al., 1983 [39] | Norway | Prospective longitudinal | 1975–1979 | Classical PKU (n = 16) | 2–6 | 7:9 | N/A | 2 to 6 |
PKU: Phenylketonuria; N/A: Not available; mHPA: mild hyperphenylalaninemia; n= sample size.