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KMID : 0918520150150020055
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Journal of the Korean Society of Inherited Metabolic Disease
2015 Volume.15 No. 2 p.55 ~ p.58
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Role of Tetrahydrobiopterin (BH4) Therapy in PKU
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Shintaku Haruo
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Abstract
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Tetrahydrobiopterin (BH4) can normalize blood phenylalanine (Phe) levels in BH4 deficiency, but typically not in phenylketonuria (PKU). In 1999, Kure et al. reported that some PKU patients showed decreased blood Phe levels after BH4 loading, and thereafter, those PKU patients were identified by neonatal PKU screening. A natural cofactor for phenylalanine hydroxylase (PAH) is a 6R-isomer of BH4, which is first synthesized in Japan as Sapropterin dihydrochloride (Biopten®) in 1982. In Japan, Biopten® is first approved for the treatment of BH4 deficiency in 1992, and then for BH4-responsive PAH deficiency (BPKU) in 2008. The discovery of BPKU has vast clinical implications. After Biopten® (Kuvan®) is available for
the treatment of BPKU, the QOL of both patients and their families were improved very much, since the serum phenylalanine levels were controlled within 4 mg/dL by BH4 mono-therapy with a normal diet or BH4 combined use of mild phenylalanine-restricted diet. Biopten® therapy in patients with BPKU is highly efficacious (70%) at maintaining serum Phe levels within recommended control range and provides excellent safety at least average use period of 10 years (range, 1-17 years) with no unwarranted side effects in Japan. In addition it has been confirmed that sapropterin therapy initiated before 4 years of age was very effective to maintain plasma Phe levels within the favorable range and was safe in Japanese patients with BPKU.
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KEYWORD
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PKU, Tetrahydrobiopterin, BH4 responsive hyperphenylalaninemia, Diet therapy
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