Phenylketonuria
Updates to Article Attributes
Phenylketonuria (PKU(PKU)is an inborn error of metabolism resulting from abnormal metabolism of phenylalanine. If untreated, patients can develop central nervous system impairment.
Epidemiology
PKU is inherited as an autosomal recessive disorder with an incidence of 1 in 10,000. It is more common in Caucasians 1,5.
Clinical presentation
Children with PKU are generally healthy at birth and develop normally in the early course of the disease. However, if not treated they eventually develop 6:
- microcephaly
- athetosis
- spasticity
- tremor
- seizures
- behavioural and psychological problems
- eczema
Pathology
PKU is inherited in an autosomal recessive pattern and is due to a mutation in the PAH gene 6. The mutation results in a deficiency of the hepatic enzyme phenylalanine hydroxylase which converts the amino acid phenylalanine, a large neutral amino acid to tyrosine. The resultant accumulation phenylalanine in the blood competes for transport across the blood-brain barrier with other amino acids via the large neutral amino acid transporter. As a result, the availability of other large neutral amino acids in neurons is decreased to the brain resulting in impaired neurotransmitter and protein synthesis 2.
Radiographic features
MRI
-
T2/FLAIR:
- high signal in affected areas
- occurring firstly in the periventricular/parieto-occipital white matter before eventually affecting the subcortical white matter (due to hypomyelination and oedema 6)
- atrophy and compensatory ventricular dilatation may occur eventually
- DWI: reduced diffusion in acutely affected areas 4
- MR spectroscopy: phenylalanine peak at 7.37 ppm 6
Treatment and prognosis
Treatment is with a phenylalanine-restricted diet 3 with the avoidance/restriction of foods such as breast milk, meat, nuts, dairy products and starchy foods (e.g. potatoes, bread) 5. Traditionally this has been enforced only during childhood, but recent evidence suggests lifelong dietary restriction is probably worthwhile 5. Reversal of neuroimaging changes are possible after adherence to a phenylalanine-restricted diet are possible 6.
-<p><strong>Phenylketonuria (PKU) </strong>is an inborn error of metabolism resulting from abnormal metabolism of phenylalanine. If untreated, patients can develop central nervous system impairment. </p><h4>Epidemiology</h4><p>PKU is inherited as an autosomal recessive disorder with an incidence of 1 in 10,000. It is more common in Caucasians <sup>1,5</sup>. </p><h4>Clinical presentation</h4><p>Children with PKU are generally healthy at birth and develop normally in the early course of the disease. However, if not treated they eventually develop <sup>6</sup>:</p><ul>-<li>microcephaly</li>- +<p><strong>Phenylketonuria </strong>(<strong>PKU</strong>)<strong> </strong>is an inborn error of metabolism resulting from abnormal metabolism of phenylalanine. If untreated, patients can develop central nervous system impairment. </p><h4>Epidemiology</h4><p>PKU is inherited as an autosomal recessive disorder with an incidence of 1 in 10,000. It is more common in Caucasians <sup>1,5</sup>. </p><h4>Clinical presentation</h4><p>Children with PKU are generally healthy at birth and develop normally in the early course of the disease. However, if not treated they eventually develop <sup>6</sup>:</p><ul>
- +<li><a title="Microcephaly" href="/articles/microcephaly">microcephaly</a></li>
-<li>seizures</li>- +<li><a title="Seizures" href="/articles/seizures">seizures</a></li>
-</ul><h4>Pathology</h4><p>PKU is inherited in an autosomal recessive pattern and is due to a mutation in the <em>PAH</em> gene <sup>6</sup>. The mutation results in a deficiency of the hepatic enzyme phenylalanine hydroxylase which converts the amino acid phenylalanine, a large neutral amino acid to tyrosine. The resultant accumulation phenylalanine in the blood competes for transport across the <a href="/articles/blood-brain-barrier">blood-brain barrier</a> with other amino acids via the large neutral amino acid transporter. As a result, the availability of other large neutral amino acids in neurons is decreased to the brain resulting in impaired neurotransmitter and protein synthesis <sup>2</sup>.</p><h4>Radiographic features</h4><h5>MRI</h5><ul>- +</ul><h4>Pathology</h4><p>PKU is inherited in an autosomal recessive pattern and is due to a mutation in the <em>PAH</em> gene <sup>6</sup>. The mutation results in a deficiency of the hepatic enzyme phenylalanine hydroxylase which converts the <a title="Amino acids" href="/articles/amino-acids-1">amino acid</a> phenylalanine, a large neutral amino acid to tyrosine. The resultant accumulation phenylalanine in the blood competes for transport across the <a href="/articles/blood-brain-barrier-3">blood-brain barrier</a> with other amino acids via the large neutral amino acid transporter. As a result, the availability of other large neutral amino acids in neurons is decreased to the brain resulting in impaired neurotransmitter and protein synthesis <sup>2</sup>.</p><h4>Radiographic features</h4><h5>MRI</h5><ul>
-</ul><h4>Treatment and prognosis</h4><p>Treatment is with a phenylalanine-restricted diet <sup>3</sup> with the avoidance/restriction of foods such as breast milk, meat, nuts, dairy products and starchy foods (e.g. potatoes, bread) <sup>5</sup>. Traditionally this has been enforced only during childhood, but recent evidence suggests lifelong dietary restriction is probably worthwhile <sup>5</sup>. Reversal of neuroimaging changes are possible after adherence to a phenylalanine-restricted diet are possible <sup>6</sup>. </p>- +</ul><h4>Treatment and prognosis</h4><p>Treatment is with a phenylalanine-restricted diet <sup>3</sup> with the avoidance/restriction of foods such as breast milk, meat, nuts, dairy products and starchy foods (e.g. potatoes, bread) <sup>5</sup>. Traditionally this has been enforced only during childhood, but recent evidence suggests lifelong dietary restriction is probably worthwhile <sup>5</sup>. Reversal of neuroimaging changes are possible after adherence to a phenylalanine-restricted diet <sup>6</sup>. </p>
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