Phenylketonuria is rare genetic disease caused by mutation in gene of phenylalanine (Phe) hydroxylase that converts Phenylalanine into tyrosine. The absence of this enzyme leads to elevation and accumulation of Phenylalanine and, increased phenylketones in urine (hence PKU), and also leads to decrease myelin formation, dopamine, norepinephrine, and serotonin production.
Phenylketonuria worldwide affects about 1 in 12,000 babies.
In Egypt the incidence rate reported 1 : 3000 (0.03%), The actual prevalence of PKU in this study were 1/3000. This is higher than that reported by Temtamy25, who found in a pilot study on 15,000 newborns in 3 governorates in Egypt that the incidence of PKU was 1/ 7500 . The latest consensus in Egypt showed that at least one million babies are born every year.
Phenylalanine hydroxylase deficiency (PAH deficiency) causes a spectrum of disorders, including classic phenylketonuria (PKU).
A rarer form of hyperphenylalaninemia is tetrahydrobiopterin deficiency, which occurs when the PAH enzyme is normal, and a defect is found in the biosynthesis or recycling of the cofactor tetrahydrobiopterin (BH4).
Elevations of phenylalanine in the plasma depend on the degree of enzyme deficiency. In patients with severe PAH deficiency (previously referred to classic phenylketonuria ), plasma phenylalanine levels on unrestricted diet usually exceed 20 mg/dL (\>1,200 μmol/L). In affected infants with plasma concentrations \>20 mg/dL, excess phenylalanine is metabolized to phenylketones (phenylpyruvate and phenylacetate) that are excreted in the urine, giving rise to the term phenylketonuria (PKU).
If left untreated and not detected early , irreversible damage may occur due to the accumulation of Phenylalanine and its metabolites in the body and will affect the growth and development of patients .
Without treatment most children develop profound and irreversible intellectual disability, seizures, hyperactive behavior with autistic features, psychiatric symptoms, eczema, musty body odor, and light pigmentation.
Newborn screening is performed to detect the disease and initiate treatment before any damage is done. The blood sample is usually taken by heel prick, typically performed 2-7 days after birth. This test can reveal elevated phenylalanine levels after one or two days of normal infant feeding. PKU is commonly included in the newborn screening panel of many countries and Egypt , with varied detection techniques. Most babies are screened for PKU soon after birth.
If left untreated and not detected early , irreversible damage may occur due to the accumulation of Phenylalanine and its metabolites in the body and will affect the growth and development of patients .
Without treatment most children develop profound and irreversible intellectual disability, seizures, hyperactive behavior with autistic features, psychiatric symptoms, eczema, musty body odor and light pigmentation.
Newborn screening is performed to detect the disease and initiate treatment before any damage is done. The blood sample is usually taken by heel prick, typically performed 2-7 days after birth. This test can reveal elevated phenylalanine levels after one or two days of normal infant feeding. PKU is commonly included in the newborn screening panel of many countries and Egypt , with varied detection techniques. Most babies are screened for PKU soon after birth.
Treatment is with a diet low in foods that contain phenylalanine and special supplements. Babies should use a special formula with a small amount of breast milk. The diet should begin as soon as possible after birth and be continued for life. People who are diagnosed early and maintain a strict diet can have normal health and a normal life .
The target of the treatment is to reach optimal health ranges of phenylalanine (or "target ranges") are between 120 and 360 µmol/L or equivalently 2 to 6 mg/dL, and aimed to be achieved during at least the first 10 years, to allow the brain to develop normally.
The dietary restriction in phenylketonuria should be only in protein diet (phenylalanine),while fat and carbohydrate diet don't need to be restricted.
Lifelong treatment will provide the best effect on growth and development, prevents neurocognitive impairment and abnormal executive functioning and helps maintaining mental health.
Anthropometric measures are important for evaluating the growth development and nutritional status of infants with phenylketonuria.
The dietary restriction in phenylketonuria should be only in protein diet (phenylalanine),while fat and carbohydrate diet don't need to be restricted.
Lifelong treatment will provide the best effect on growth and development, prevents neurocognitive impairment and abnormal executive functioning and helps maintaining mental health.
Anthropometric measures are important for evaluating the growth development and nutritional status of infants with phenylketonuria.
Intelligence and mental development in PKU PKU results, in untreated patients, a profound intellectual disability and more subtle cognitive deficits in individuals who were treated early and continuously. The assessment of intellectual functioning in PKU has been an important target outcome variable since the implementation of neonatal PKU screening programs in the 1960s . Research on intellectual functioning in individuals with PKU has played a significant role in guiding treatment recommendations and improving outcomes.
Brumm and Grant conducted a literature review examining the relationship between intellectual outcome and treatment parameters including initiation of treatment, duration of treatment, and blood phenylalanine (Phe) levels from infancy through adulthood. While current PKU treatment practices have eliminated severe neurological and cognitive impairment, evidence suggests that intellectual functioning, although typically within the average range when PKU is treated early and continuously, may not be maximized under the current definition of well-controlled PKU, which is based on blood Phe levels.
