New treatments for PKU
As long-term dietary modification is difficult and a great hassle, PKU patients may risk being outcasted by friends and families due to their abnormal dietary needs, there is a need for alternative modes of treatments.
Large neutral amino acids
The large neutral amino acids (LNAA) including phe compete at the blood brain barrier for entry to the brain through the same transporter (LAT1). Increasing the concentration of LNAA in the blood therefore reduces phe entry to the brain. There is a similar mechanism in the gut, and absorbed phe is lower if LNAA are supplemented in generous amounts. It is unlikely that LNAA given as sole treatment without phe restriction could replace diet in childhood but may be a useful approach for adults.
Sapropterin therapy (Tetrahydrobiopterin, BH4, trade name: Kuvan)
Sapropterin is an important cofactor of PAH in the degradation of phe. Due to the lack of PAH expression in PKU patients, the degradation of phe is also reduced as a result. We can reconstitute the lack of PAH expression through Sapropterin therapy. Thus resulting in reduction of phe levels. However this is more likely to work for cases of mild PKU rather than classic PKU as the later PKU may have absolutely no expression of PAH. it has been estimated that 80% of those with mild PKU and 40% of those with classical PKU weill benefit from this treatment. To be sure of the patients' response to this treatment, Genotyping could be used to predict the response but should not be assumed.
Gene therapy
The most promising results come from experiments using recombinant adeno-associated virus vector in which long-term correction without adverse effects has been reported in the mouse model (PKUenu2). There are no human gene therapy studies yet.
Liver Transplant
A liver transplantation can effectively provide a healthy PAH activity in a PKU patient. But the complications of this procedure makes transplantation an unrealistic treatment option for PKU
You mentioned about 2 types of PKU: Mild & Classic, but what is the difference between the two types and is there any difference in terms of the special diet that they have to take for eg. the dosage etc? Further are what are the difference in the symptoms that they experience?
ReplyDelete-Mandy & Xin Yan
Okay..Classic PKU occurs when Phenylalanine Hydroxylase(PAH)is mutated and Phenylalanine cannot be converted into Tyrosine. The accumulation of Phe levels in the body causes the decarboxylation and transamination of Phenylalanine. This causes high levels of Phenylalanine metabolites to build up causing retardation.
ReplyDeleteIn mild PKU, the PAH enzyme is not entirely mutated and hence there is a mildly elevated phenylalanine level in the body. It is not as severe as the Classic PKU.
Both types of PKU patients have regular blood checks to monitor their blood Phe levels. So their diet can be adjusted accordingly to ensure the Phe level is maintained at a appropriate level. So to sum up, there is no difference in the special diet the both groups of patients take.
And regarding the last question, I'm not getting what you're asking :/ If I'm not mistaken you want to know more on the different symptoms both groups of patients experience..If that's what you want to know here is my answer to you..The symptoms are the same.
Hope that answers all your queries.
:)
- Zhi Zheng & Mukesh
How liver transplantation process is performed in phenylketonuria patient? what is the molecular pathway involved?
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