What are the consequences of a deficiency in phenylalanine hydroxylase?
Signs and symptoms include microcephaly, epilepsy, severe intellectual disability, and behavior problems. The excretion of excessive Phe and its metabolites can create a musty body odor and skin conditions such as eczema.
What is the expected result of a deficiency in the enzyme phenylalanine hydroxylase in children with phenylketonuria PKU )?
Without the enzyme necessary to break down phenylalanine, a dangerous buildup can develop when a person with PKU eats foods that contain protein or eats aspartame, an artificial sweetener. This can eventually lead to serious health problems.
How common is phenylalanine hydroxylase deficiency?
Phenylalanine hydroxylase deficiency is an autosomal recessive disorder that results in intolerance to the dietary intake of the essential amino acid phenylalanine. It occurs in approximately 1:15,000 individuals.
What is the role of phenylalanine hydroxylase in PKU?
Phenylalanine hydroxylase is responsible for the conversion of phenylalanine to another amino acid, tyrosine. The enzyme works with a molecule called tetrahydrobiopterin (BH4) to carry out this chemical reaction.
How does PKU affect the body?
In a child with PKU, phenylalanine cannot be converted to tyrosine because the phenylalanine hydroxylase enzyme does not work properly. This results in dangerously high levels of phenylalanine that build up in the blood and become toxic to the brain and nervous system.
What are the clinical consequences of PKU and why should it be detected as early as possible?
PKU does not usually cause any symptoms if treatment is started early. Without treatment, PKU can damage the brain and nervous system, which can lead to learning disabilities. Other symptoms of untreated PKU include: behavioural difficulties such as frequent temper tantrums and episodes of self-harm.
What is phenylketonuria PKU How important is the synthesis of correct proteins?
Phe is an essential amino acid obtained exclusively by the diet or by proteolysis. It is crucial for protein synthesis, as well as for the synthesis of Tyr and its derivatives, such as dopamine, norepinephrine, and melanin [1,2]….Table 2.
| Reference | Sample | Findings |
|---|---|---|
| Justice and Hsia, 1965 | Mouse brain | ↓ 5THD |
How does phenylalanine affect the brain?
The high plasma phenylalanine concentrations increase phenylalanine entry into brain and restrict the entry of other large neutral amino acids. In the literature, emphasis has been on high brain phenylalanine as the pathological substrate that causes mental retardation.
Does PKU cause behavioral problems?
As children and adolescents, patients with PKU may have learning difficulties, school problems, decreased motivation, less social competence, irritability, hyperactivity, mood disorders, and poor self esteem.
Why does PKU cause neurological symptoms?
PKU affects the brain. When neurotransmitters are not made in the right amounts, the brain cannot function properly. High blood Phe levels can cause disruptions in neurotransmitters like serotonin and dopamine, which are important for mood, learning, memory, and motivation.
What happens to excessive phenylalanine accumulation in the blood of a phenylketonuria patient?
Because nerve cells in the brain are particularly sensitive to phenylalanine levels, excessive amounts of this substance can cause brain damage. Classic PKU, the most severe form of the disorder, occurs when phenylalanine hydroxylase activity is severely reduced or absent.
What systems are affected by PKU?
How does PKU affect physical development?
The developing baby in the uterus can be exposed to very high levels of phenylalanine. This can cause low birth weight, slow growth, small head, behavior problems, and heart disorders.
What is the pathophysiology of phenylketonuria?
Pathophysiology of PKU When one of several gene mutations results in deficiency or absence of phenylalanine hydroxylase, dietary phenylalanine accumulates; the brain is the main organ affected, possibly due to disturbance of myelination.
Can PKU cause ADHD?
Individuals with PKU and ADHD seem to have low levels of DA in common, causing the hypodopaminergic state found in both disorders to be a possible link between these two conditions, and individuals with PKU could have a greater predisposition to the development of ADHD.
Which body function is affected when one lacks phenylalanine?
Infants with PKU lack the ability to produce the enzyme phenylalanine hydroxylase, which converts phenylalanine to tyrosine. The resulting buildup of phenylalanine in blood and tissues is correlated to low IQ and leads to severe mental retardation.
Can PKU cause schizophrenia?
Recessive mutations in the Phenylalanine hydroxylase (PAH) gene predispose to phenylketonuria (PKU) in conjunction with dietary exposure to phenylalanine. Previous studies have suggested PAH variations could confer risk for schizophrenia, but comprehensive follow-up has not been reported.
Is there a difference between BH4 deficiency and PKU deficiency?
Differential diagnosis of PKU and BH4 deficiency. It is positive in all BH4-deficient patients and in certain mild PKU patients but cannot always differentiate between PKU responders and BH4-deficient patients. 3 Mild PAH mutations with a substantial residual enzyme activity are most likely to demonstrate increased activity in the presence of BH4.
What is the normal range of Phe in PKU?
Individuals with PAH deficiency and plasma Phe between 600 and 1200 μmol/L (10-20 mg/dL) on an unrestricted diet have not been extensively studied. However, it is well documented that individuals with classic PKU who have levels in this range have both acute and chronic neuropsychological problems.
How is PAH deficiency diagnosed?
PAH deficiency can be detected by newborn screeningin virtually 100% of cases based on the presence of hyperphenylalaninemia using tandem mass spectrometry on a blood spot obtained from a heel prick. The diagnosis of PAH deficiency is established in a probandwith:
What is the best treatment for classic PKU?
Treatment of Classic PKU. The generally accepted goal of treatment for individuals with PAH deficiency is normalization of the concentrations of Phe (phenylalanine) and Tyr (tyrosine) in the blood and thus prevention of the cognitive deficits that are attributable to this disorder [ Burgard et al 1999 ].