The Prevalence of Phenylketonuria in Arab Countries, Turkey, and Iran: A Systematic Review

Table 2

Illustration categorization of the studies based on the type of screening used. Prevalence as % and rate per 100.000 neonates and or sick/symptomatic subjects were computed. NA: information is not available; among citizen only, -calculated prevalence, and information. Remarks column indicates the way of prevalence/incidence estimated by articles if different from computed and states any self-computing prevalence and correction made in this review.

Type	Study and country setting	Age at sampling	Sample size	Prevalence									Consanguinity	Remarks
				Classical PKU			Biopterin defect (BH4)			HPA (mild and moderate)
				Number of cases	(%)	Per 100,000 neonates/sick	Number of cases	(%)	Per 100,000 neonates/sick	Number of cases	(%)	Per 100,000 neonates/sick
National NBS program	[6]; Saudi Arabia; 2017,; King Faisal Specialist Hospital and Research Center, King Salman Center for Disability Research, King Saud bin Abdulaziz for health Science, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, King Fahad Medical City, Children Hospital, Armed Forces Medical Service Directorate, Security Forces Hospital	After 24 hr. of birth	775000	53	0.0068	6.84	NA	—	—	NA	—	—	No information	Incidence Rate reported in article as 1 : 14245 and should be corrected to 1 : 14623
	[15]; United Arab of Emirates, 2000,; Ministry of Health, National screening center, Tawam Hospital	5th day for discharged newborns and before discharge for those admitted for >5 days	138718	7	0.0050	5.05	NA	—	—	NA	—	—	No information	Incidence Rate reported in article as 1 : 20050 and should be corrected to 1 : 19816.9
	[16]; United Arab of Emirates, 2014,; Ministry of Health, National screening center, Tawam Hospital	3rd day after birth (≥48 hr) and before discharge for those admitted for >3 days	750365	51	0.0068	6.80	1.00	0.00013	0.13	NA	—	—	No information	PKU incidence rate reported in article as 1 : 14544 and should be corrected to 1 : 14713 not including BH4 defect and to 1 : 14430.1 if including BH4 dependent PKU case
	[17]; Arab of Emirates, ,; United Arab Emirates University, Al-Ain, Tawam Hospital	48 hr. of age and before discharge for those admitted for >3 days	136049	11	0.0080	8.09	NA	—	—	NA	—	—	Among PKU not indicated. But among all 55 metabolic cases detected inclusive PKU consanguinity was 81.5%	Self-calculated prevalence among citizens.; Article estimates overall incidence of metabolic disorders included in program. Correction of some of all Emirates live birth in Table 1 (2011–2014) to be 136058 instead of 136049
	[18]; Turkey, ,; Hacettepe University, Departments of Nutrition and Metabolism, Molecular biology, Dietetics and Neonatology, Ankara	Samples collected before discharge & test repeated if collected <24 h	576122	96	0.0166	16.66	1.00	0.00017	0.17	46.0	0.008	7.98	45.7% of marriages among PKU families were consanguineous. 30.9% were first degree relative marriages, 5.6% second degree, 7.2 others and 54.3 were nonconsanguineous	Incidence of classical PKU in article table reported as 1 : 6000. For persistent HPA as 1 : 12500. The total of both as 1 : 4500 that should be corrected to 1 : 4057
Regional/governorate newborn screening program	[19]; Palestine Gaza Strip, ,; Biology Department, Al-Azhar University, College of Public health, Gaza Central Laboratories, Ministry of Health	Average age 13.5 days	1022207	65	0.0063	6.36	NA	—	—	NA	—	—	60% of PKU parents were first cousins, while 7.7% with no consanguinity	Correction: article used the total population live birth in calculating prevalence. However, it should be calculated using total number of newborn screened in 2000 which is mentioned as 13175 and including the 11 cases that had been excluded due to death. So, corrected prevalence should be % or ~577 : 100000
	[20]; Iraq, Sulaimani City, 2015,; Iraq, Department of Pediatrics, School of Medicine, University of Sulaimani and Sulaimani Pediatric Teaching Hospital	3–10 days	8255	1	0.0121	12.11	NA	—	—	NA	—	—	The parents of this case were consanguineous	Incidence in article reported as 1.2 : 10000 neonates
	[21]; Iraq, Baghdad/Al-Karkh Directorate, ,; Alkindy College of Medicine, University of Baghdad, AlKarkh Health Directorate, Ministry of Health	Within 3–5 days up to 2 months	80409	6	0.0075	7.46	NA	—	—	NA	—	—	No information	Self-calculated Prevalence. Article did not report prevalence of PKU. Data extracted from table & figure then calculated
	[22]; Iran, Fars province, Shiraz, 2009,; Human Genetics Research Group, Iranian Academic Center for Education, Culture and Research, Paramedical School of Shiraz University of Medical Science, Iran Center of Blood Transfusion of Shiraz, Department of Mathematics, Yasuj University	72 hours after birth	70477	15	0.0213	21.28	NA	—	—	NA	—	—	The frequency of familial marriages in these children parents were 86.6%	Incidence rate reported in article as 1 : 4698
	[23]; Iran, Fars province, 2010,; Pediatric Endocrinologist, PKU Center, Naderkazemi Clinic, Department of Pediatrics, Department of Medical Technology, Paramedical School, Neonatal Screening Laboratory in Shiraz University of Medical Sciences	3–5 days after birth	175235	28	0.0160	15.98	NA	—	—	1.0	0.001	0.57	No information	Reported incidence of PKU was 1.6 : 10000. It also indicate incidence of malignant PKU to be 3 : 100. Two patients had transient HPA.
	[24]; Iran, Mazandaran Province,; Department of Pediatrics, School of Medicine, Clinical Research Development Unit of Bou Ali-Sina Hospital, Diabetes Research Center, Research Development Unit of Referral Laboratory, Deputy of Health, Deputy of Health Management, Department of Pharmacology, all from Mazandaran University of Medical Science.; Deputy of Health, Babol University of Medical Science	During the days 3–5 after birth	407244	6	0.00147	1.47	NA	—	—	21	0.005	5.16	Parental relationship observed in 16 cases (53.6%)	PKU incidence was reported to be 0.66 in 10,000, while nonclassic PKU cases were not detected
PKU selective screening for newborns	[25]; Saudi Arabia, Aramco, 2010,; Saudi Aramco Medical Facilities in the Eastern Province	Not indicated	165530	12	0.0072	7.25	4.00	0.0024	2.41	NA	—	—	Almost all of detected cases were consanguineous	Incidence Rate reported in article for classical PKU is 7 : 100000 live birth and for BH4 defect is 2 : 100000
	[26]; Egypt, Menofiya, 2009,; Pediatrics Department, National Liver Institute, Menoufiya University, Biomedical Genetics Department, National Research Center	Mean age 9.3 ± 2.43 days	3000	1	0.0333	33.33	NA	—	—	NA	—	—	Positive consanguinity was found in 57% of the samples	Incidence Rate reported in article as 1 : 3000 (0.03%)
	[27]; Turkey, 1986,; Department of Metabolism and Department of Neonatology, Institute of Child Health, Hacettepe University, General Maternity Hospital, Ankara	Samples collected before discharge & test repeated if collected <24 h	20979	8	0.0381	38.13	NA	—	—	4.0	0.019	19.07	No information	Article reported Incidence of typical PKU as 1 : 2622 and that for HPA as 1 : 5243 and the overall is 1 : 1747
	[28]; Lebanon, ,; Department of Pathology and Laboratory Medicine and Pediatrics, American University of Beirut	2-3 days	9117	1	0.0110	10.97	NA	—	—	1.0	0.011	10.97	No information	Self-calculated Prevalence. Article did not state prevalence of PKU. Data extracted from table and calculated for both classical PKU and HPA.
	[29]; Lebanon, 2015,; Medical genetics Unit in Saint –Joseph University, Epidemiology and Population Studies Department and Department Of Pediatrics and Adolescent Medicine at the American University of Beirut, Faculty of Science at the Lebanese University	Not indicated	126000	18	0.0143	14.29	7.00	0.0055	5.55	NA	—	—	No information
	[30]; Iran, ,; Human Genetic and Anthropology Unit, Department of Human Ecology, School of Public Health and Department of Pediatrics, Medical School, University of Tehran	4–8 days	8633	1	0.0116	11.58	NA	—	—	7.0	0.081	81.08	No information	Reported incidence was 1 : 8000, should be corrected to 1 : 8633. Mild HPA cases normalized after retesting
Selective screening of sick newborns or/and infants, children and adults	[31]; Bahrain, 2013,; Department of Molecular Medicine, Colleges of Medicine and Medical Science, AGU, Manama	3–90 days	1986	3	0.1511	151.06	NA	—	—	NA	—	—	21 out of 25 diagnosed patients had consanguineous parents	Article stated detection rate as 1 : 662 (incidence among screened) and incidence rate among all live birth during this period as 1 : 22188
	[32]; Kuwait, 1988,; Department of Clinical Biochemistry, Al-Sabah Hospital	13% neonates, 26% infants (<1 year of age), 43% older children and 18% adults (>12 year)	800	9	1.1250	1125.00	NA	—	—	1.0	0.125	125.0	Out of 9 patients, 8 had consanguineous parent and one nonconsanguineous	Benign HPA only one case. Author only included 9 PKU in prevalence calculation
	[33]; Oman, ,; Department of Biochemistry, Department of Child Health, Sultan Qaboos University	No age	1100	8	0.7273	727.27	3.00	0.2727	272.72	NA	—	—	9 out of 11 PKU patients had consanguineous parents	Self-calculated Prevalence. Article did not report prevalence of PKU. Data extracted from table and calculated for both classical and BH4 dependent PKU
	[34]; Egypt, Cairo, ,; Department of Pediatric Neurology, Department of Pediatric Genetics and Department of Clinical and Chemical Pathology in Cairo University. Inherited Metabolic Disease Unit, Cairo University Children Hospital	2.5 months to 6.6 years	3380	100	2.9586	2958.58	NA	—	—	NA	—	—	Out of 203 different metabolic disorder detected, 178 of patients were born to consanguineous parent’s ~ 88%	Article stated prevalence of PKU from total abnormal 203 cases detected . Corrected prevalence should be
	[35]; Jordan, 2012,; Department of Pediatrics, Metabolic Genetics Clinic, Queen Rania Al-Abdullah Children Hospital, King Hussein Medical Center	One to 50 months	212	17	8.0189	8018.87	NA	—	—	NA	—	—	137 out of 151 families having different metabolic disorder showed parental consanguinity
	[36]; Lebanon, ,; Department of Pediatrics and Adolescent Medicine and Department of Pathology and Laboratory Medicine at the American University of Beirut Medical Center	2 months to 21 years	2921	90	3.0811	3081.1	NA	—	—	NA	—	—	Included other metabolic disorders were 60% and parents were first cousins in 35%	Article stated prevalence of PKU from total abnormal 203 cases detected . Corrected prevalence should be . Author mentioned that during last three years of the study, 49750 newborns were screened out of which 13 cases of PKU were detected without reporting prevalence. So self-calculated Prevalence of PKU from this information is 0.026%
	[37]; Iraq, 2013,; Department of Pediatrics, College of Medicine, Baghdad University and Children Welfare Teaching Hospital Medical City Complex	>1 year and <5 years	63	7	11.111	11111.1	NA	—	—	NA	—	—	All PKU cases were related to consanguineous marriages
	[38]; Iraq, 2016,; Child Welfare Teaching Hospital and Al-Emamain Al Kadhemyian Teaching Hospital, Baghdad	9.3% neonates (0–30 days of age), 34% (>1–5 years), 9.3% >5 years.	1758	19	1.0807	1080.8	NA	—	—	1.0	0.057	56.88	Out of 1758 sick patients, 174 cases had consanguineous parents (9.8%)
	[39]; Iran, Shiraz, ,; Department of Biochemistry, Department of Pediatric, Shiraz University of Medical Sciences	Not indicated	106151	29	0.0273	27.3	NA	—	—	10.0	0.009	9.42	34 patients with PKU out of the 43 had consanguineous parents	Reported incidence of PKU in article after Jan 1996 is 1 : 3672. However, it was mentioned that total number of PKU cases detected out of 1044 patient selectively screened was 43 cases. 33 classical PKU and 10 milder cases. So corrected calculated prevalence of classical PKU among selectively screened is or 3161 : 100000
Selective screening for both newborns and sick newborns and/or infants, children and adults	[40]; Kuwait, ,; Department of Pharmaceutical Chemistry and Pharmacy Practice, Faculty of Pharmacy at Kuwait University and Department of Pediatrics at Sabah Hospital
	Among newborns; Among sick	Not indicated	1520; 362	0; 1	0.000; 0.2762	0.00; 276.2	NA; NA	—; —	—; —	3.0; 0.0	0.197; 0.0	197.37; 0.00	No information	Self-calculated Prevalence among sick subjects. Article did not report prevalence of PKU. Data extracted from table and calculated. For all those screened (sick or newborns). Overall classical PKU prevalence can be estimated as
	[41]; Egypt, ,; Clinical and Chemical Pathology and Pediatrics Departments, Faculty of Medicine, Cairo University and Ministry of Health and Population
	Among neonates; Among sick/symptomatic	3–7 days; 3 months to 15 years	16000; 550	4; 14	0.0250; 2.5455	25.0; 2545.4	NA	—	—	—	—	—	No information	Self-calculated prevalence among sick subjects. Article report incidence of PKU among newborns as 1 : 4000. For all those screened (sick & newborns), overall classical PKU prevalence can be estimated as
	[42]; Egypt, ,; Clinical and Chemical Pathology and Department of Pediatrics in Cairo University, Inherited Metabolic Disease Unit, Cairo University Children Hospital
	Among neonates; Among sick/symptomatic	3–7 days; 1 week to 15 years	25276; 3900	5; 116	0.0198; 2.9744	19.8; 2974.3	NA	—	—	NA	—	—	No information	Article stated that PKU cases among newborns are 1 : 5000. Also, estimated birth prevalence among newborns and sick subjects as percent from number of abnormal cases not total screened as 38.5% and 49.3%, respectively. Corrected estimates should be done using total number screened as calculated in table
	[43]; Turkey, Ankara, ,; Institute of Child Health, Department of Metabolism, Hacettepe University, Ankara, Department of Pediatrics, Free University of Berlin
	Among Selected high risk infants; Among healthy newborn	Not indicated	6050; 170466	116; 39	1.9174; 0.0229	1917.4; 22.9	NA; NA	—; —	—; —	NA; 19.0	—; 0.011	—; 11.15	In infant’s selective screening, there was parental consanguinity in 72% of the all 225 detected cases	Reported incidence of typical PKU among newborns as 1 : 4370, persistent HPA as 1 : 8971 and overall incidence as 1 : 2874. The total should be corrected to 1 : 2939
Selective screening for sick children and adults from mental retardation institutes	[43]; Turkey, Ankara, 1990,; Institute of Child Health, Department of Metabolism, Hacettepe University, Ankara, Department of Pediatrics, Free University of Berlin	Not indicated	10800	510	4.7222	4722.2	NA	—	—	NA	—	—	Among mentally retarded children, 45% of cases had parental consanguinity and the rest were not
	[44]; Kuwait, 1987,; Kuwait Medical Genetics Center, Maternity Hospital	5–45 Years	451	7	1.5521	1552.1	NA	—	—	NA	—	—	Parental consanguinity in all 7 patients. In six cases parents were first cousins and in one case distant relatives but from the same tribe
	[45]; Iran, Isfahan, ,; Department of Biology, Genetics division at Isfahan University	Not indicated	611	26	4.2553	4255.3	NA	—	—	8.0	1.3	130.9	68% of the cases, parents were first cousins	Article stated the prevalence of all HPA as . Also estimated frequency of all HPA among all mentally retarded individuals in the institute as . So, the prevalence of true PKU cases among screened 611 subject was self-calculated to be 4.25%
	[46]; Iran, Tehran, 2009,; Department of Biology, Grand Vally State University, Genetic Center, Beheshti University of Medical Science in Tehran, Iran, Department of Epidemiology, School of Health and Nutrition, Shiraz University of Medical Science, Student Research Center, Tehran University of Medical Science, Department of statistics, Grand Vally state University Allendale, Mi, USA, Tehran Province Welfare and Rehabilitation Organization	Average age 13.5 days	4963	104	2.0955	2095.5	NA	—	—	21.0	0.423	423.13	No information	Article reported prevalence of classical PKU among all mentally retarded individuals in Iran as 2.1% and prevalence of mild HPA as 0.44%. The prevalence among inmates sheltered in Tehran only was 2.81% and other cities were 1.68%