CopperKettle: /* Treatment */
'''Dihydropteridine reductase deficiency''' (DHPRD) is a genetic disorder affecting the tetrahydrobiopterin (BH4) synthesis pathway, inherited in the autosomal recessive pattern. It is one of the six known disorders causing [[tetrahydrobiopterin deficiency]], and occurs in patients with mutations of the [[QDPR]] gene.
The disease presents with such symptoms as elevated levels of phenylalanine ([[hyperphenylalaninemia]]), microcephaly, hypotonus, mental retardation and [[epileptic seizure]]s.
==Diagnostics==
Besides the traditional analysis of symptoms and investigation of [[phenylalanine]] concentrations, patients suspected for DHPRD undergo the assessment of enzymatic activity using the [[dried blood spot]] method - this permits to distinquish DHPR deficiency from the other forms of BH4 deficiency.<ref name="pmid32456656">Liquid error: wrong number of arguments (given 1, expected 2)</ref>.
==Treatment==
Patients are prescribed a phenylalanine-reduced diet, with regular monitoring of phenylalanine levels in the blood. Besides the diet, a patient may be prescribed [[sapropterin]], a synthetic analogue of [[tetrahydrobiopterin]].
In order to restore dopamine levels in the central nervous system, patients are given [[L-dopa]] in conjunction with an [[Aromatic L-amino acid decarboxylase inhibitor|inhibitor of aromatic amino acid decarboxylase]] that acts outside the nervous system, so as to promote the transformation of L-dopa into dopamine inside the central nervous system, and thus to improve the efficiency of the treatment.
Since the unsufficient levels of BH4 inhibit the transformation of tryptophan into 5-hydroxytryptophan in a reaction in which BH4 serves as a cofactor of the enzyme [[TPH2|tryptophane hydroxylase 2]], patients suffer from a lack of serotonin in their CNS. In order to correct this deficiency, they are given [[5-hydroxytryptophan]].
In patients with DHPR deficiency, a pronounced lack of [[5-methyltetrahydrofolate]] (5-MTHF) is observed in the central nervous system. This condition, termed [[cerebral folate deficiency]], (CFD) is more severe in DHPRD patients than in patients with other forms of BH4 deficiency. CFD is corrected by treating patients with [[folinic acid]], a form of folate that efficiently passes the [[hematoencephalic barrier]].<ref name="pmid32456656"/><ref name="EmeryRimoinBook">(2013) Emery and Rimoin's Principles and Practice of Medical Genetics. [https://ift.tt/2NWcCef Chapter 92. Amino Acid Metabolism. 92.1.7. DHPR Deficiency], by Raymond Y.Wang, William R.Wilcox, and Stephen D.Cederbaum</ref> The use of ''[[folic acid]]'', the synthetic form of folate employed in food fortification, should be avoided because folic acid tightly binds to the [[folate receptor alpha]] and may inhibit the transport of folate into the central nervous system.
==References==
[[Category:Metabolic disorders]]
The disease presents with such symptoms as elevated levels of phenylalanine ([[hyperphenylalaninemia]]), microcephaly, hypotonus, mental retardation and [[epileptic seizure]]s.
==Diagnostics==
Besides the traditional analysis of symptoms and investigation of [[phenylalanine]] concentrations, patients suspected for DHPRD undergo the assessment of enzymatic activity using the [[dried blood spot]] method - this permits to distinquish DHPR deficiency from the other forms of BH4 deficiency.<ref name="pmid32456656">Liquid error: wrong number of arguments (given 1, expected 2)</ref>.
==Treatment==
Patients are prescribed a phenylalanine-reduced diet, with regular monitoring of phenylalanine levels in the blood. Besides the diet, a patient may be prescribed [[sapropterin]], a synthetic analogue of [[tetrahydrobiopterin]].
In order to restore dopamine levels in the central nervous system, patients are given [[L-dopa]] in conjunction with an [[Aromatic L-amino acid decarboxylase inhibitor|inhibitor of aromatic amino acid decarboxylase]] that acts outside the nervous system, so as to promote the transformation of L-dopa into dopamine inside the central nervous system, and thus to improve the efficiency of the treatment.
Since the unsufficient levels of BH4 inhibit the transformation of tryptophan into 5-hydroxytryptophan in a reaction in which BH4 serves as a cofactor of the enzyme [[TPH2|tryptophane hydroxylase 2]], patients suffer from a lack of serotonin in their CNS. In order to correct this deficiency, they are given [[5-hydroxytryptophan]].
In patients with DHPR deficiency, a pronounced lack of [[5-methyltetrahydrofolate]] (5-MTHF) is observed in the central nervous system. This condition, termed [[cerebral folate deficiency]], (CFD) is more severe in DHPRD patients than in patients with other forms of BH4 deficiency. CFD is corrected by treating patients with [[folinic acid]], a form of folate that efficiently passes the [[hematoencephalic barrier]].<ref name="pmid32456656"/><ref name="EmeryRimoinBook">(2013) Emery and Rimoin's Principles and Practice of Medical Genetics. [https://ift.tt/2NWcCef Chapter 92. Amino Acid Metabolism. 92.1.7. DHPR Deficiency], by Raymond Y.Wang, William R.Wilcox, and Stephen D.Cederbaum</ref> The use of ''[[folic acid]]'', the synthetic form of folate employed in food fortification, should be avoided because folic acid tightly binds to the [[folate receptor alpha]] and may inhibit the transport of folate into the central nervous system.
==References==
[[Category:Metabolic disorders]]
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