Phenylketonuria is an autosomal recessive genetic disorder. The estimated worldwide incidence is 1 in 10000 [1]. According to the data obtained from neonatal screening between 2000 and 2005 in the Fars province of Iran, an incidence of 1 in 4698 was reported [3] An incidence of 1 in 6662 live births was also reported in the Chaharmahalobakhtiari province of Iran between 2012 and 2015 [4]. According to another study performed between 2010 and 2011 in Yazd province on 22131 neonates, an incidence of 1.8 in 10000 births was reported. [8] Consanguinity is thought to be the most important factor regarding the higher incidence of this disease in some parts of the world [2]. Phenylketonuria is the most common disorder of amino acids metabolism [10].
Normally ingested phenylalanine is metabolized to tyrosine through the action of phenylalanine hydroxylase and a cofactor called tetrahydrobiopterin. Deficient phenylalanine hydroxylase cannot metabolize phenylalanine to tyrosine, which leads to phenylalanine accumulation in body. [11] Phenylalanine accumulation mainly damages the Brain. Normally, subsequent metabolic processes convert tyrosine to a number of metabolites including skin and hair pigments, and final metabolites are excreted from the body [30]. Over 950 genes are associated with phenylalanine hydroxylase deficiency [6]. Measuring phenylalanine blood level is a practical and reliable method to diagnose the disease and monitor the treatment course [5]. In classic phenylketonuria phenylalanine blood level is more than 20 mg/dl. Following strict specific diets in which the consumption of natural proteins is restricted and instead amino acid formulas are consumed, phenylalanine intake is limited and brain damage is prevented. The specific diet must be followed throughout life [7]. Every 1.66 mg/dl increase in phenylalanine blood level is associated with 1.3 up to 3.1 points reduction in Intelligence Quotient (IQ) [5]. Phenylketonuria is the first metabolic and genetic disorder which has been successfully treated [12]. According to the Iranian national phenylketonuria guideline, the accepted phenylalanine level is 2 – 6 mg/dl and 2 – 10 mg/dl for those under 12 years old and those over 12 years old respectively.
Normally a limited amount of phenylalanine is metabolized to phenylketones, including phenylpyruvate, phenylacetate and phenyllactate; in patients having phenylketonuria, high amounts of phenylketones are produced. High phenylpyruvate level interferes with myelin synthesis in brain, leading to mental retardation. Another proposed cause of mental retardation in these patients is deficient synthesis of neurotransmitter dopamine, which is normally synthesized from tyrosine. Normally the only source of tyrosine production in human body is the metabolism of phenylalanine trough the action of phenylalanine hydroxylase; as a result tyrosine is an essential amino acid in patients having phenylketonuria which must be obtained through appropriate diet.
The early weeks of life is a critical period for the developing brain of the infant, and feeding infants having phenylketonuria with breast milk and normal formulas could cause irreversible neurologic damage, and later treatments and therapeutic diets would not be effective.
Untreated infants present later in life with developmental delay, vomiting, growth retardation, seizure, blond hair and blue eyes. During early childhood, microcephaly, restlessness, attention deficit, repetitive limbs movement and mental retardation are among other manifestations. The presence of excessive amount of phenylalanine metabolites is the cause of musty urine odor in untreated patients. Urticarial skin Rash is one of the other presentations of untreated patients.
The disease could be screened from day two of life onward, using a blood or urine sample. A phenylalanine blood level of 20 mg/dl or more is suggestive of phenylketonuria. As a result of early diagnosis and administration of specific formulas to affected infants, affected children could have normal intelligence and brain function. The goal of treatment is to reduce phenylalanine blood level to a safe amount. During infancy and childhood, patients can consume a variety of foods including vegetables, fruits, starch, fat, rice, breads and a limited amount of grains. Blood phenylalanine level should be checked regularly. According to blood phenylalanine level, the diet of each patient must be planned by a dietician. The recommended diet must be followed throughout life [30]. It is notable that despite early diagnosis and appropriate therapeutic diet, patients having phenylketonuria may have problems in maintaining attention and poor academic performance. [13]
Assessing possible factors that might affect patients` adherence to the therapeutic diet could be an important progress in achieving better care for them. According to a systematic review article by Medford et al. age, sex, family composition including separated parents or cohabitant parents, parents` educational level, child knowledge about phenylketonuria, parent employment or occupational status, and the number of siblings with phenylketonuria are factors that have significant positive correlation with phenylalanine blood level. The authors of this review article state that there is a paucity of studies examining the potential demographic or psychosocial influences on metabolic control of patients having phenylketonuria, which could be due to the rarity of this disease and small sampling pool. [7]
In 2011 during a study performed on 105 children having phenylketonuria at Mofid hospital, Tehran, the following factors were found to be correlated with the metabolic control of these patients. Metabolic control was better in those under 12 years old. The number of siblings having phenylketonuria, divorced parents, and occupational status of parents were among other affecting factors. The authors concluded that the social status of patients affect phenylalanine level to some degree. [18]
In a study performed by Mahmoudi-Gharaei et al., 49 care givers of children having phenylketonuria who were presented to a psychiatry outpatient clinic were assessed. Based on the results of this study, 57.1 per cent and 50.1 percent of caregivers had depression and anxiety respectively; and employment status played a meaning full role regarding their mental health. The authors recommended performing similar studies in other parts of Iran. [19]
Considering the lack of similar studies in the eastern part of Iran, this study was conducted to assess the effect of a number of suggested socioeconomic factors that are presumed to be correlated with phenylalanine blood level.