Sepiapterin deficiency

Fig. 6.1.8a-c HPLC of the yellow-fluorescing pterins, a Standard mixture b control cerebrospinal fluid (CSF) c CSF sepiapterin reductase deficiency. HS -Hydroxyse-piapterin, S sepiapterin, X xanthopterin... 

Bonafe L, Thony B, Penzien JM, Czarnecki B, Blau N (2001) Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine neurotransmitter deficiency without hyperphenylalaninemia. Am J Hum Genet 69 269-277... 

Blau N, Bonafe L, Thony (2001) Tetrahydrobiopterin deficiencies without hyperphenyl-alaninemia diagnosis and genetics of Dopa-responsive dystonia and sepiapterin reductase deficiency. Mol Genet Metab 74 172-185... 

Besides the involvement in the de novo biosynthesis of BH4, SR may also participate in the pterin salvage pathway by catalyzing the conversion of sepiapterin (Figure 14, 47) into 7,8-dihydrobiopterin (46) that is then transformed to BH4 by dihydrofolate reductase (DHFR EC 1.5.1.3). Both reactions consume NADPH. Although SR is sufficient to complete the BH4 biosynthesis, a family of alternative NADPH-dependent aldo—keto reductases, including carbonyl reductases (CR), aldose reductases (AR), and the 3a-hydroxysteroid dehydrogenase type 2 (AKR1C3) may participate in the diketo reduction of the carbonyl side chain in Moreover, based on the discover) of the autosomal recessive deficiency for SR, which presents... 

IWo disorders of BH4 metabolism may present without hyperphenylalaninemia. These are Dopa-responsive dystonia (DRD Segawa disease) and sepiapterin reductase (SR) deficiency. While DRD is caused by a mutation in the GTPCH gene and is inherited in an autosomal dominant manner, SR deficiency is an autosomal recessive trait. Both diseases evidence severe biogenic amines deficiencies. DRD usually presents with a dystonic gait and diurnal variation. At least two reports describe heteroallelic patients with DRD suggesting a wide spectrum of GTPCH variants. 

Curtius, H.-Ch., Niederwieser, A., Viscontini, M., Otten, A., Schaub, J., Scheibenreiter, S. and Schmidt, H. (1979), Atypical phenylketonuria due to tetrahydrobiopterin deficiency. Diagnosis and treatment with tetrahydrobiopterin, dihydrobiopterin, and sepiapterin. Clin. Ckim. Acta, 93,251. 

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