Tetrahydrobiopterin therapy of atypical phenylketonuria due to defective dihydrobiopterin biosynthesis.

Schaub, J.; Däumling, S; Curtius, Hans−Christoph; Niederwieser, A.; Bartholomé, K.; Viscontini, M.; Schircks, Bernhard; Bieri, Jost H.

doi:10.1136/adc.53.8.674

Cited by 59 publications

(19 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Oral administration was not adequately tested because traditional beliefs suggested that BH, was unlikely to be absorbed. However, Schaub et al (26) have recently shown the oral BH4 was effective in a patient with defective BH4 synthesis. Oral administration of biopterin had no effect on phenylalanine metabolism despite changes in blood and urine Crithidia activity that strongly suggest that the biopterin was absorbed.…”

Section: Discussionmentioning

confidence: 99%

“…. , Measurement of serum phenylalanine before, and 6 hr after, administration of BH, (2 mg/kg iv or im) seems a very simple method of recognizing cases of MHPA among babies with a positive Guthrie test (7,8) applicable in patients with DHPR deficiency and in those with defective BH4 synthesis (26). The test requires no new laboratory methods, and a result is obtained within 1 day and before dietary treatment is started.…”

Section: Discussionmentioning

confidence: 99%

“…Deficiency of DHPR has been defined recently (15,18,25). Some patients with PKU have proved to have normal levels of both DHPR and PH (3,25,26) and presumably have a defect in de novo synthesis of' BH,. These defects in BH4 synthesis and metabolism have been found among patients with PKU who have shown progressive cerebral degeneration despite early initiation of dietary treatment.…”

Section: Case Imentioning

confidence: 99%

See 2 more Smart Citations

Malignant Hyperphenylalaninemia—Clinical Features, Biochemical Findings, and Experience with Administration of Biopterins

et al. 1979

View full text Add to dashboard Cite

Pediat. Res. 13: 1 150-1 155 (1979) Summary has been attributed to defective production of neurotransmitters Four cases of malignant hyperphenylalaninemia (MHPA) are described. Pretreatment serum phenylalanine levels were 1.5, 3.0, 2.4, and 0.9 mmoles/l. Dihydropteridine reductase (DHPR) deficiency was proven in one patient by assays on cultured fibroblastic cells and was presumed in her sibling and in another deceased patient whose parents' fibroblastic cells show approximately 50% of normal enzyme activity. DHPR and phenylalanine hydroxylase deficiency were excluded by assays on liver obtained a t autopsy in the 4th patient. Parenteral administration of tetrahydrobiopterir (BH4) corrected the hyperphenylalaninemia and increased the levels of catecholamines and 5-hydroxy-indoles in the one patient studied in life, but BH4 did not reach the cerebrospinal fluid. A 3-wk course of BH4 therapy had no clinical effect. Oral biopterin was absorbed and excreted in the urine, but did not alter the serum phenylalanine level. The frequency of MHPA in Australia was estimated as 7 in 258 patients with phenylketonuria.derived from hydroxylation of tyrosine and of tryptophan (3, 4). The results of treatment with L-dopa and 5-hydroxytryptophan support this contention (2, 3. 7).Four patients with MHPA seen in Melbourne since 1963 are presented. One patient has been shown to have DHPR deficiency and her sister is presumed to have died of this defect. Both parents of another baby had DHPR levels in the heterozygote range suggesting DHPR deficiency as the cause of her death. The 4th baby had neither PH or DHPR deficiency and defective BH4 synthesis is presumed.Detailed metabolic studies, especially related to BH4 are presented in the one DHPR deficient patient diagnosed in life. The lowering of serum phenylalanine achieved by BH4 administration in this patient is proposed as a test for identification of young babies with MHPA.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Case Imentioning

confidence: 99%

See 1 more Smart Citation

Malignant Hyperphenylalaninemia—Clinical Features, Biochemical Findings, and Experience with Administration of Biopterins

et al. 1979

View full text Add to dashboard Cite

show abstract

“…In this enzyme the same active center base (B -) is shown to catalyze the abstraction as a proton of both the 1'-H (+), as well as the 2'-H (---+) of the side chain. The enzymes which catalyze the two-step reduction of PPHL (4) to BH4 (7) are 'PPH4 reductase' and sepiapterin reductase (SR), respectively. The sequence of the two steps, i.e.…”

mentioning

confidence: 99%

“…All recently published results [21-311 are indeed consistent with this. It is generally accepted that NHzTP (1) is converted to PPH4 (4) in the presence of Mgz+ by the heat-stable 'Enzyme A' or 'sepiapterin synthase A' from D . melanogaster [14,22,261, 'fraction AT from chicken kidney [15], and 'SSE-1' [32] or 'dyspropterin synthetase' from silkworm larvae [30].…”

mentioning

confidence: 99%

Biosynthesis of tetrahydrobiopterin. Purification and characterization of 6-pyruvoyl-tertrahydropterin synthase from human liver

et al. 1986

View full text Add to dashboard Cite

6-Pyruvoyl-tetrahydropterin synthase, which catalyzes the first step in the conversion of 7,s-dihydroneopterin triphosphate to tetrahydrobiopterin, was purified approximately 140,000-fold to apparent homogeneity from human liver. The molecular mass of the enzyme is estimated to be 83 kDa. 7,X-Dihydroneopterin triphosphate was a substrate of the enzyme in the presence of Mg2+, and the pH optimum of the reaction was 7.5 in Tris HCI buffer. The K, value for 7,fLdihydroneopterin triphosphate was 10 pM. The product of this enzymatic reaction was the presumed intermediate 6-pyruvoyl-tetrahydropterin. This latter compound was converted to tetrahydrobiopterin in the presence of NADPH and partially purified sepiapterin reductase from human liver. The conditions and the effect of N-acetylserotonin on this reaction, and on the formation of the intermediates 6-(1 '-hydroxy-2'-oxopropyl)-tetrahydropterin and 6-( 1'0x0-2'-hydroxypropy1)-tetrahydropterin have been studied.

show abstract

Cerebrospinal Fluid Biopterin Is Decreased in Alzheimer's Disease

Kay¹,

Milstien²,

Kaufman³

et al. 1986

Archives of Neurology

View full text Add to dashboard Cite

Tetrahydrobiopterin therapy of atypical phenylketonuria due to defective dihydrobiopterin biosynthesis.

Cited by 59 publications

References 9 publications

Malignant Hyperphenylalaninemia—Clinical Features, Biochemical Findings, and Experience with Administration of Biopterins

Malignant Hyperphenylalaninemia—Clinical Features, Biochemical Findings, and Experience with Administration of Biopterins

Biosynthesis of tetrahydrobiopterin. Purification and characterization of 6-pyruvoyl-tertrahydropterin synthase from human liver

Cerebrospinal Fluid Biopterin Is Decreased in Alzheimer's Disease

Contact Info

Product

Resources

About