China
Africa
Explore chapters and articles related to this topic
Hyperphenylalaninemia and defective metabolism of tetrahydrobiopterin
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Deficiency of PTPS is the most common of the defects in biopterin metabolism, approximating 60 percent of the patients. The majority have had the typical form, but in ∼15 percent, presentation is atypical. The typical patients have high levels of neopterin and low biopterin in the urine (Table 16.1) and CSF. These patients have the highest neopterin levels and the highest ratios of neopterin to BH4 of all the abnormalities in pterin metabolism. The atypical patients have been referred to as peripheral because the CSF is normal, but with time it can become abnormal [6, 43]. Clinical presentation in these patients is milder and response to treatment more satisfactory. A 20 mg/kg load of BH4 leads to a rapid decrease in the plasma concentration of phenylalanine.
Enzymes
Published in Stephen W. Carmichael, Susan L. Stoddard, The Adrenal Medulla 1986 - 1988, 2017
Stephen W. Carmichael, Susan L. Stoddard
An extensive review of the regulation of tetrahydrobiopterin biosynthesis and cofactor replacement by tetrahydropterins was published by Nichol, Smith, Reinhard et al. (1988). Among other things, they pointed out that the regulation of tetrahydrobiopterin biosynthesis is best illustrated in cells containing TH, such as adrenal chromaffin cells. Changes in tissue levels of the cofactor appear to be correlated with the rate of catecholamine synthesis. The evidence that some degree of biopterin cofactor deficiency is associated with certain psychiatric and neurologic disorders indicates the need for a more detailed understanding of these complex relationships.
Neurogenetics
Published in John W. Scadding, Nicholas A. Losseff, Clinical Neurology, 2011
Sonia Gandhi, Sarah Tabrizi, Nicholas Wood
In patients with dystonia that is highly L-dopa responsive, a diagnosis of dopa-responsive dystonia (DRD/DYT5) should be considered. DRD is most commonly autosomal dominant with reduced penetrance, and caused by mutations in the gene for GTP-cycohydrolase 1, the enzyme required for tetrahydrobiopterin synthesis. This biopterin is in turn the cofactor for tyrosine hydroxylase, the enzyme required for dopamine synthesis. Mutations in the gene for tyrosine hydroxylase have also been identified that give rise to an autosomal recessive form of DRD.
Clinical, biochemical and molecular spectrum of mild 6-pyruvoyl-tetrahydropterin synthase deficiency and a case report
Published in Fetal and Pediatric Pathology, 2021
Boyan Song, Zhijun Ma, Wei Liu, Lihong Lu, Yongjian Jian, Lu Yu, Zhihui Wan, Xiaofei Yue, Yuanyuan Kong
At 49 days after birth, the results of urine pterin spectrum analysis were as follows: neopterin: 3.44 mmol/molCr (reference range: 1.21–2.92 mmol/molCr), biopterin: 0.21 mmol/molCr (reference range: 0.42–1.92 mmol/molCr), B%: 5.75% (reference range: 19.8%−50.3%; B%=100 × biopterin/(biopterin + neopterin)). DHPR analysis showed that the activity was 1.65 nmol/min 5 mm disc (reference range: 1.02–3.35 nmol/min 5 mm disc), which suggested that the patient had PTS deficiency. In the subsequent three measurements after a low phenylalanine diet, the blood phenylalanine levels fluctuated between 12.1–29.2 mmol/L (Fig. 1), which were below the lower limit of the reference range. Then the low phenylalanine diet was ceased. As the blood phenylalanine level was not high, a BH4 load test was not carried out. The parents refused to provide consent for the cerebrospinal fluid extraction and drug therapy.
Effects Of Endothelin-1 On Intracellular Tetrahydrobiopterin Levels In Vascular Tissue
Published in Scandinavian Cardiovascular Journal, 2018
Ruha Cerrato, Mark Crabtree, Charalambos Antoniades, Karolina Kublickiene, Ernesto L. Schiffrin, Keith M. Channon, Felix Böhm
We went on to investigate biopterin levels in ET-TG mice. The advantage of using ET-TG mice is that the long-term effects on biopterins of increased local endogenous ET-1 production in endothelial cells could be determined in aorta, lungs as well as plasma. However, even though there is 3-fold higher vascular tissue ET-1 mRNA content and 7-fold higher ET-1 plasma levels in this model [11], we could not see any effects on biopterins in these tissues. It may be due to that this phenotype is relatively healthy without overt atherosclerosis. In addition, oxidative stress and NADPH oxidase is increased in this model, which together with our findings collectively suggests that ET-1 affects NADPH oxidase rather than eNOS uncoupling in this model.
Urine as a biological modality for colorectal cancer detection
Published in Expert Review of Molecular Diagnostics, 2020
Subashini Chandrapalan, Ramesh P Arasaradnam
Neopterin is a metabolite of biopterin released from activated macrophages. Thus, it is a marker of cellular immunity. Weiss et al. [34] showed high Neopterin levels (above 220 μmol/mol of creatinine) were significantly (P = 0.0034) associated with poor prognosis in CRC in comparison to the group who had Neopterin levels below that level. Another retrospective study in a population with advanced or metastatic CRC showed that the survival of these patients was significantly longer when the urinary Neopterin concentrations were less than 214 μmol/mol creatinine [35]. A larger Hordaland health study [36] and a study by Aleksandrova and colleagues [37] also confirmed similar findings in plasma Neopterin levels.