Abstract
Background: The Sapropterin dihydrochloride enzyme cofactor, a synthetic analog form of 6R‑BH4, was offered as an oral treatment for
hyperphenylalaninemia. The sapropterin dihydrochloride role in patients with phenylketonuria (PKU) is to activate the endogenous phenylalanine
hydroxylase (PAH) and to restore partially the oxidative metabolism of phenylalanine (Phe), when patients have insufficiency or lack of
tetrahydrobiopterin. The sapropterin dihydrochloride anticipated to restore PAH activity through providing an exogenous source of the lost or
deficient cofactor. Aim of Study: This study aims to evaluate the effects and clinical significance of tetrahydrobiopterin supplementation in
hyperphenylalaninemia. Patients and Methods: This study describes the use of tetrahydrobiopterin in 58 patients with hyperphenylalaninemia
treated before the age of 15 years with the use of tetrahydrobiopterin loading test. More than 30% decrement in Phe consider positive.
Results: Fifty‑eight patient been enrolled in this prospective study as follows; seven patient non PKU hyperphenylalaninemia (Phe level <600 μM),
13 patients mild to moderate PKU (Phe level between 600 and 1200 μM) and 38 with classic PKU (Phe level equal or above 1200 μM). The mean
of Phe at the diagnosis was 377.00 ± 150.240 μM, 843.00 ± 133.899 μM and 1513.736 ± 274.372 μM sequentially. The response to treatment
with tetrahydrobiopterin was inversely related to the level of Phe where its 100% in non PKU hyperphenylalaninemia, 70% in mild‑to‑moderate
PKU and 16% in classic PKU. Tetrahydrobiopterin therapy significantly enhanced dietary Phe tolerance and permitted a Phe‑free medical
formula to be discontinued in a significant number of patients in whom phenylalaninemia within therapeutic target (120–300 μM) were
achieved. Tetrahydrobiopterin displays the safety and usefulness of this treatment for patients mild PKU. Conclusions: Tetrahydrobiopterin
therapy should be tried in all patients with hyperphenylalaninemia and/or PKU as it may significantly decrease the Phe level and improvement
his milestone moreover safe in mild PKU.
hyperphenylalaninemia. The sapropterin dihydrochloride role in patients with phenylketonuria (PKU) is to activate the endogenous phenylalanine
hydroxylase (PAH) and to restore partially the oxidative metabolism of phenylalanine (Phe), when patients have insufficiency or lack of
tetrahydrobiopterin. The sapropterin dihydrochloride anticipated to restore PAH activity through providing an exogenous source of the lost or
deficient cofactor. Aim of Study: This study aims to evaluate the effects and clinical significance of tetrahydrobiopterin supplementation in
hyperphenylalaninemia. Patients and Methods: This study describes the use of tetrahydrobiopterin in 58 patients with hyperphenylalaninemia
treated before the age of 15 years with the use of tetrahydrobiopterin loading test. More than 30% decrement in Phe consider positive.
Results: Fifty‑eight patient been enrolled in this prospective study as follows; seven patient non PKU hyperphenylalaninemia (Phe level <600 μM),
13 patients mild to moderate PKU (Phe level between 600 and 1200 μM) and 38 with classic PKU (Phe level equal or above 1200 μM). The mean
of Phe at the diagnosis was 377.00 ± 150.240 μM, 843.00 ± 133.899 μM and 1513.736 ± 274.372 μM sequentially. The response to treatment
with tetrahydrobiopterin was inversely related to the level of Phe where its 100% in non PKU hyperphenylalaninemia, 70% in mild‑to‑moderate
PKU and 16% in classic PKU. Tetrahydrobiopterin therapy significantly enhanced dietary Phe tolerance and permitted a Phe‑free medical
formula to be discontinued in a significant number of patients in whom phenylalaninemia within therapeutic target (120–300 μM) were
achieved. Tetrahydrobiopterin displays the safety and usefulness of this treatment for patients mild PKU. Conclusions: Tetrahydrobiopterin
therapy should be tried in all patients with hyperphenylalaninemia and/or PKU as it may significantly decrease the Phe level and improvement
his milestone moreover safe in mild PKU.
Keywords
BH4
hyperphenylalaninemia
kuvan
phenylketonuria
sapropterin dihydrochlorid