Difference between revisions of "Phenylketonuria 2012"
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| + | '''Phenylketonuria''' (PKU) is an autosomal recessive inherited disorder. It is monogenetic and the connected gene (PAH) is located at the chromosome 12, which encodes for the hepatic enzyme [http://en.wikipedia.org/wiki/Phenylalanine_hydroxylase phenylalanine hydroxylase](PAH). People who suffer from this disorder have a strongly decreased activity of this enzyme and therefore suffer from the toxic effects of the accumulated [http://en.wikipedia.org/wiki/Phenylalanine phenylalanine](Phe) which leads mostly to mental retardation but also to certain other [[Phenylketonuria#Symptoms|symptoms]]. Due to the ongoing development for [[Phenylketonuria#Treatment|treatment]] and adhering to dietary restrictions the patients can avoid most effects of the disease. |
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| − | | Name = Phenylketonuria |
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| − | '''Phenylketonuria''' (PKU) is an autosomal recessive inherited disorder. It is monogenetic and the connected gene (PAH) is located at the chromosome 12, which encodes for the hepatic enzyme [http://en.wikipedia.org/wiki/Phenylalanine_hydroxylase phenylalanine hydroxylase](PAH). People who suffer from this disorder have a strongly decreased activity of this enzyme and therefore suffer from the toxic effects of the accumulated [http://en.wikipedia.org/wiki/Phenylalanine Phenylalanine](Phe) which leads mostly to mental retardation but also to certain other [[Phenylketonuria#Symptoms|symptoms]]. Due to the ongoing development for [[Phenylketonuria#Treatment|treatment]] the patient can avoid most effects of the disease. |
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==Summary== |
==Summary== |
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| − | Phenylketonuria is a widely distributed an known disease, with rarely severe effects (with the right [[Phenylketonuria#Treatment|treatment]]). It affects the digestion of |
+ | Phenylketonuria is a widely distributed an known disease, with rarely severe effects (with the right [[Phenylketonuria#Treatment|treatment]]). It affects the digestion of phenylalanine(Phe) mostly through decreasing the efficiency of the Enzyme phenylalanine hydroxilase (PAH). The main danger with this disease is the accumulation of Phe in the blood, which is toxic in high doses. Those will lead to mental retardation and other [[Phenylketonuria#Symptoms|symptoms]] |
==Symptoms== |
==Symptoms== |
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| + | ==Diagnosis== |
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| + | If the disease is recognised and treated within the first days of a newborn, before toxic amounts of phenylalanine can build, patients can avoid the symptoms of PKU. Newborn screenings generally carried out between day 2 and day 5 include a test for PKU. |
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| + | The most simple test is a bacterial inhibition assay (Guthrie test) that uses ''Bacillus subtilis'', a bacteria that needs phenylalanine to grow. More reliable tests employ mass spectrometry, checking not only the level of Phe but also the tyrosine/phenylalanine ratio. |
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| + | To differentiate patients with high Phe levels due to PKU from patients with BH4 deficiency, a cofactor of PAH, a 'BH4 loading test' can be performed. This |
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| + | also detects the subgroup of PKU patients that can be treated with BH4, since the cofactor also has some chaperone activity. |
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==Treatment== |
==Treatment== |
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| − | uiui |
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| + | The most effective way to treat the symptoms of PKU is to avoid food rich in phenylalanine. This requires a strict diet excluding all animal protein, dairy products and many vegetable food and including medical food, especially milk powder for newborns low in Phe. |
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| + | 10-60 % of the patients respond to treatment with ''tetrahydrobiopterin'' (BH4), the cofactor of PAH, or a synthetic alternative. This cofactor possesses chaperone activity and apparently can restore PAH function for certain mutations. |
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| + | Treatments in development are enzyme substitution therapy and gene therapy. The enzyme phenylalanine ammonia lyase (PAL) catalyses Phe to ammonia and non-toxic trans-cinnamic acid. In mice it lowered the Phe level safely and persistently and is in clinical trials for humans since 2009. |
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==References== |
==References== |
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Revision as of 10:44, 20 April 2012
Phenylketonuria (PKU) is an autosomal recessive inherited disorder. It is monogenetic and the connected gene (PAH) is located at the chromosome 12, which encodes for the hepatic enzyme phenylalanine hydroxylase(PAH). People who suffer from this disorder have a strongly decreased activity of this enzyme and therefore suffer from the toxic effects of the accumulated phenylalanine(Phe) which leads mostly to mental retardation but also to certain other symptoms. Due to the ongoing development for treatment and adhering to dietary restrictions the patients can avoid most effects of the disease.
Summary
Phenylketonuria is a widely distributed an known disease, with rarely severe effects (with the right treatment). It affects the digestion of phenylalanine(Phe) mostly through decreasing the efficiency of the Enzyme phenylalanine hydroxilase (PAH). The main danger with this disease is the accumulation of Phe in the blood, which is toxic in high doses. Those will lead to mental retardation and other symptoms
Symptoms
Diagnosis
If the disease is recognised and treated within the first days of a newborn, before toxic amounts of phenylalanine can build, patients can avoid the symptoms of PKU. Newborn screenings generally carried out between day 2 and day 5 include a test for PKU. The most simple test is a bacterial inhibition assay (Guthrie test) that uses Bacillus subtilis, a bacteria that needs phenylalanine to grow. More reliable tests employ mass spectrometry, checking not only the level of Phe but also the tyrosine/phenylalanine ratio.
To differentiate patients with high Phe levels due to PKU from patients with BH4 deficiency, a cofactor of PAH, a 'BH4 loading test' can be performed. This also detects the subgroup of PKU patients that can be treated with BH4, since the cofactor also has some chaperone activity.
Treatment
The most effective way to treat the symptoms of PKU is to avoid food rich in phenylalanine. This requires a strict diet excluding all animal protein, dairy products and many vegetable food and including medical food, especially milk powder for newborns low in Phe.
10-60 % of the patients respond to treatment with tetrahydrobiopterin (BH4), the cofactor of PAH, or a synthetic alternative. This cofactor possesses chaperone activity and apparently can restore PAH function for certain mutations.
Treatments in development are enzyme substitution therapy and gene therapy. The enzyme phenylalanine ammonia lyase (PAL) catalyses Phe to ammonia and non-toxic trans-cinnamic acid. In mice it lowered the Phe level safely and persistently and is in clinical trials for humans since 2009.
