Phenylketonuria (PKU) is a genetic metabolic disorder characterized by complete or near-complete deficiency of an important enzyme known as phenylalanine hydroxylase (PAH). PAH is the enzyme necessary to convert the amino acid phenylalanine into the amino acid tyrosine. Tyrosine is necessary for the production of certain hormones, neurotransmitters, and melanin. Patients with PKU must have restricted dietary phenylalanine to live without PKU complications. These complications include mental retardation, hypopigmentation, and psychological problems such as agoraphobia. However, agoraphobia is noticed in patients with or without dietary treatment. Seizures, delayed development, and movement disorders are also common. Affected individuals may have a musty or mouse-like odor due to excess phenylalanine in the body.
It is found that approximately 1% of the mentally retarded patients are affected by PKU. The diet can be gradually enlarged, but metabolic control must be performed during the first ten years of life. Phenylalanine is toxic to fetal development, therefore pregnant women with high phenylalanine level must have special diet and they must be observed to save fetus life. Pharmacological doses of tetrahydrobiopterin (BH4), a cofactor of PAH, are found to be effective for some patients with PKU.
Classic PKU affects about one of every 10,000 to 20,000 Caucasian or Oriental births. PKU is rare in blacks. A high incidence is reported in Turkey, regions of Northern and Eastern Europe, the Yemenite Jewish population, Italy, Estonia, China, and former Yugoslavia. A low prevalence is reported in Finland.
Al-Arrayed (2006) (Al-Arrayed SS. Personal communication, Dubai, 2006) indicated that PKU occurs in Bahrain at an approximate incidence of 1/10,000 births.
Shawky et al. (2002) analyzed the polymorphism caused by the variation in the number of STRs as markers to detect PKU carriers in Egyptian families. The study included 16 PKU index cases, four affected sibs and three affected first cousins; 37 PKU carriers and 15 normal individuals as controls. Among the subjects, only eight STR alleles were identified. These alleles differed only in the number of the basic TCTA repeat and they had allele sizes starting from 230 to 258 bp. Thus, Shawky et al. (2002) suggested that the polymorphic nature of this system is a consequence of insertions or deletions of four basepair repeat units. The 250-bp allele was the commonly associated with wild-type chromosomes (42%), whereas the 246-bp allele was the most frequent on mutant chromosomes (35.7%). In addition, the 254-bp allele had the second highest frequency (25%) on mutant chromosome.
[See also: Kuwait > Bender et al., 1994].
Teebi et al. (1987) identified phenylketonuria cases in Kuwait through conducting a study on 451 institutionalized mentally retarded subjects aged 5-45 years. Seven Kuwaiti subjects (4 males and 3 females) from 451 patients were found to suffer from phenylketonuria and they were all born to consanguineous parents.
Yadav and Reavey (1988) presented a summary of the results of quantitative amino acid analysis in 800 subjects over a three-year period in Al-Sabah Hospital, Kuwait. Nine cases of phenylketonuria were identified, one benign hyperphenylalaninemia. Later, Yadav et al. (1992) chose 187 subjects for examination of amino acid diseases out of 430 mentally retarded institutionalized subjects in Kuwait over a four year period. Serum samples were collected from 69 males and 118 females and analyzed using quantitative amino acid analysis. The analysis revealed 11 cases with various aminoacidopathies including eight cases with phenylketonuria.
Usha et al. (1992) reported the case of a first case 22 year old woman with phenylketonuria (PKU); the first case described in Bedouins.
Bender et al. (1994) studied the PAH gene in four Kuwaiti and four Egyptian families with at least one child affected with. Digestion with MspI revealed a polymorphism, previously been described among Black Americans, in one Egyptian family as well as one of the controls.
Mubashir et al. (1996) reported four Bedouin sibs with phenylketonuria (PKU) from Al-Jahra region in Kuwait. They were born to double first cousin Bedouin parents and grand-parents.
Samilchuk (2005) studied single gene disorders in Kuwait, and named PKU as the most common single gene metabolic disorder in the country.
In a retrospective analysis of IEMs diagnosed over a 12-year period (1998-2010) in a hospital in Lebanon, Karam et al. (2013) found 90 patients diagnosed with phenylktonuria. The median age of diagnosis was 1 year and 9-months.
Joshi et al. (2002) carried out a retrospective analysis of all patients born with inborn errors of metabolism in Oman between June 1998 and December 2000. Among the 82 patients, three were diagnosed with phenylketonuria [CTGA Database Editor's note: Computed annual incidence rate is 2.4/100,000]. Few years later, Joshi and Venugopalan (2007) conducted a study over a seven year period (1998-2005) to evaluate the clinical profiles of 166 neonates at high risk of having inborn errors of metabolism using Tandem Mass Spectrometry (TMS). Out of a total of 38 neonates with positive TMS results, one baby, aged 21 days was diagnosed with classical PKU. The baby was born to consanguineous parents and had a family history of the condition.
Al-Riyami et al. (2012) reported on the types and patterns of IEMs encountered in a sample of 1100 high-risk neonates referred to SQU Hospital in Oman over a 10-year period (1998-2002). MS/MS was used to analyze blood samples from heel pricks. A total of 119 of these neonates were found to test positive for an IEM. PKU was detected in eight neonates (six males, two females), belonging to five families. There was a family history of the condition in six of the patients, while six had consanguineous parents.
In 2003, the Hamad Medical Corporation, in partnership with the University Children's Hospital of Heidelberg built a comprehensive newborn screening program. Between December 2003 and July 2006, Lindner et al. (2007) investigated 25,214 neonates born in Qatar for inborn errors of metabolism and endocrine disorders. One neonate was diagnosed with PKU, whereas another neonate was found to have hyperphenylalaninemia. The NBS result was available at 5-days of age for the former patient, and treatment was initiated at 8-days of age. The latter patient did not receive any treatment.
Moammar et al. (2010) reviewed all patients diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. During the study period, 165530 Saudi infants were born, of whom a total of 248 newborns were diagnosed with 55 IEM. Almost all patients were born to consanguineous parents. Aminoacidopathies were diagnosed in 38 out of 248 cases (16%). Among them, twelve cases from three families were found to have classic phenylketonuria (PKU). The estimated incidence of this condition is 7 in 100,000 live births.
Al-Hosani et al. (2003) performed a study to evaluate the progress of the UAE national newborn screening program and to determine the incidence of phenylketonuria (PKU) in the UAE. Over a period of six years, 13,8718 newborns were screened and of those, seven confirmed PKU cases were detected with an incidence 1:20050 for PKU.
Avigad et al. (1987) reported a deletion of exon 3 responsible for all PKU cases among the Yemenite Jews. Using a molecular probe that detects carriers of the deletion, they identified 5 carriers among 200 randomly selected volunteers from this community who were not related to the known PKU families. Although the deleted gene was traced to 25 different locations throughout Yemen, family histories and official documents of the Yemenite Jewish community showed that the common ancestor of all the carriers of this defect lived in Sanaa, the capital of Yemen, before the eighteenth century.