Detection of Sepiapterin in CSF of Patients with Sepiapterin Reductase Deficiency

Zorzi, Giovanna; Redweik, U.; Trippe, H; Penzien, Johann; Thöny, Beat; Blau, Nenad

doi:10.1006/mgme.2001.3273

Cited by 38 publications

(22 citation statements)

References 14 publications

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“…The disease is hard to diagnose due to lack of peripheral markers and brain MRI is normal in most cases. CSF reveals low HVA and 5-HIAA and high levels of biopterin and dihydrobiopterin with the presence of sepiapterin (Zorzi et al 2002). As in our case the diagnosis can be also be established by mutation analysis and confirmed by documenting low SR activity in skin fibroblast cultures.…”

Section: Discussionsupporting

confidence: 73%

“…Collectively, the disorders that respond to levodopa are termed dopa-responsive dystonias (DRD), the best known being GTP cyclohydrolase deficiency (Segawa's disease). In addition, defects in tyrosine hydroxylase, aromatic L-amino acid decarboxylase and sepiapterin reductase (SR) can also lead to DRD (Zorzi et al 2002;Friedman et al 2006; Th€ ony and Blau 2006; Abeling et al 2006;Neville et al 2005). No association with peroxisomal disorders has ever been described.…”

Section: Introductionmentioning

confidence: 99%

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Levodopa Response Reveals Sepiapterin Reductase Deficiency in a Female Heterozygote with Adrenoleukodystrophy

et al. 2011

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We report a 4-year-old girl heterozygous for X-linked adrenoleukodystrophy (ALD) who displayed doparesponsive motor symptoms and was subsequently diagnosed with sepiapterin reductase deficiency (SPR; OMIM 182125). Her father and paternal uncle had known ALD, and she was found to have elevated plasma very long chain fatty acids and a mutation in the ABCD1 gene. She had language delay, severe hypotonia and abnormal eye movements and responded dramatically to a trial of levodopa (4 mg/kg per day). Two mutations within the gene for sepiapterin reductase were found and cultured skin fibroblasts demonstrated near zero activity of the enzyme. This case illustrates the importance of treatment trials that may give rise to biochemical clues to the underlying diagnosis, and the need to continue to search for diagnoses despite a misleading family history.

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Levodopa Response Reveals Sepiapterin Reductase Deficiency in a Female Heterozygote with Adrenoleukodystrophy

et al. 2011

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“…19,20 Investigation of their skin fibroblasts, however, provided evidence of an enzymatic block in the biosynthesis of BH 4 and impaired sepiapterin reductase (SR) activity, a finding supported by the detection of causative mutations in the SPR gene of both patients and family members 21 and by high levels of sepiapterin in the CSF. 22 The absence of HPA and the presence of normal urinary pterin pattern and of normal pterin metabolism in erythrocytes was explained by alternative pathways of BH 4 biosynthesis in pheripheral and neuronal tissues. In the final two-step reaction, SR activity may be substituted by aldose reductase (AR), and/or carbonyl reductase (CR), and dihydrofolate reductase (DHFR) in the former, whereas in the latter only AR and CR are present (see Fig.…”

Section: B H 4 F U N C T I O N S a N D D E F I C I E N C Ymentioning

confidence: 98%

Dihydropteridine reductase deficiency in man: From biology to treatment

Ponzone

Spada

Ferraris

et al. 2003

Medicinal Research Reviews

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In 1975, dihydropteridine reductase (DHPR) deficiency was first recognized as a cause of tetrahydrobiopterin (BH(4)) deficiency, leading to hyperphenylalaninemia (HPA) and impaired biogenic amine deficiency. So far, more than 150 patients scattered worldwide have been reported and major progresses have been made in the understanding of physiopathology, screening, diagnosis, treatment, and molecular genetics of this inherited disease. Present knowledge on different aspects of DHPR deficiency, largely derived from authors' personal experience, is traced in this article.

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“…The only evidence for a regulatory role of SR in NO synthesis comes from a study by Gao and coworkers, where knockdown of SR in endothelial cells was associated with dramatic decreases in both BH4 content and NO levels (82). Evidence for the sepiapterin synthesis pathway in humans comes from a recent study of rare patients with SR deficiency, in which sepiapterin levels were elevated in cerebrospinal fluid (CSF), which suggests endogenous production of sepiapterin (344).…”

Section: Sepiapterin Reductasementioning

confidence: 99%

Tetrahydrobiopterin in Cardiovascular Health and Disease

Bendall

Douglas

McNeill

et al. 2014

Antioxidants & Redox Signaling

194

187

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Tetrahydrobiopterin (BH4) functions as a cofactor for several important enzyme systems, and considerable evidence implicates BH4 as a key regulator of endothelial nitric oxide synthase (eNOS) in the setting of cardiovascular health and disease. BH4 bioavailability is determined by a balance of enzymatic de novo synthesis and recycling, versus degradation in the setting of oxidative stress. Augmenting vascular BH4 levels by pharmacological supplementation has been shown in experimental studies to enhance NO bioavailability. However, it has become more apparent that the role of BH4 in other enzymatic pathways, including other NOS isoforms and the aromatic amino acid hydroxylases, may have a bearing on important aspects of vascular homeostasis, inflammation, and cardiac function. This article reviews the role of BH4 in cardiovascular development and homeostasis, as well as in pathophysiological processes such as endothelial and vascular dysfunction, atherosclerosis, inflammation, and cardiac hypertrophy. We discuss the therapeutic potential of BH4 in cardiovascular disease states and attempt to address how this modulator of intracellular NO-redox balance may ultimately provide a powerful new treatment for many cardiovascular diseases. Antioxid. Redox Signal. 20, 3040-3077.

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Detection of Sepiapterin in CSF of Patients with Sepiapterin Reductase Deficiency

Cited by 38 publications

References 14 publications

Levodopa Response Reveals Sepiapterin Reductase Deficiency in a Female Heterozygote with Adrenoleukodystrophy

Levodopa Response Reveals Sepiapterin Reductase Deficiency in a Female Heterozygote with Adrenoleukodystrophy

Dihydropteridine reductase deficiency in man: From biology to treatment

Tetrahydrobiopterin in Cardiovascular Health and Disease

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