Primapterinuria: A New Variant of Atypical Phenylketonuria

Blau, Nenad; Curtius, Hans−Christoph; Kuster, Thomas; Matasović, A.; Schoedon, Gabriele; Dhondt, Jean-Louis; Guibaud, P; Giudici, Tullio A.; Blaskovics, M.

doi:10.1007/978-94-009-1069-0_44

Cited by 13 publications

(8 citation statements)

References 4 publications

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“…The first patients were described by Dhondt et al (IS) and Blaskovics and Giudici (16). A loading test with BH4 was the first indication that primapterin may derive from biopterin (17). Furthermore, 7,8-dihydrobiopterin and sepiapterin given orally resulted in a significant increase in biopterin and primapterin., whereas the ratio remained between 1.0 and I.S after loading (\8).…”

Section: Biochemical Observationmentioning

confidence: 99%

“…it will be hepful to have recombinant protein available, free from any contamination, to perform in vitro studies with PAH. In addition, the newly described form of hyperphenylalaninemia characterized by 7-pterin excretion was proposed to be due to a defect in PHS/PCD activity (13)(14)(15)(16)(17). The isolation of the DNA encoding this protein will allow to further investigate the enzymatic defects in such patients on the molecular level.…”

Section: Loading Test With Bh4mentioning

confidence: 99%

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Tetrahydrobiopterin Deficiency: From Phenotype to Genotype

et al. 1993

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SummaryAs a result of the selective screening worldwide during the last 18 years, approximately 250 patients with tetrahydrobiopterin deficiency were discovered. Most patients suffer from 6-pyruvoyl tetrahydropterin synthase deficiency (58%), followed by dihydropteridine reductase deficiency (35%), GTP cyclohydrolase I deficiency (3%), and "primapterinuria" (4%). The patients can be treated with neurotransmitter precursors, as well as with tetrahydrobiopterin. However, data on long term treatment are still scarce and it is therefore of great value to investigate all newborns with even mild hyperphenylalaninemia. Cloning of the enzymes involved in the biosynthesis and regeneration of tetrahydrobiopterin makes them to be easily accessible for biochemical and biological studies. So far, all proteins expressed heterologous are active in E. coli. Cloning of the wild type gene and mutant analysis of patients allow the rapid identification of the defective gene on the molecular level.

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Section: Biochemical Observationmentioning

confidence: 99%

Section: Loading Test With Bh4mentioning

confidence: 99%

Tetrahydrobiopterin Deficiency: From Phenotype to Genotype

et al. 1993

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“…These patients display, besides HPA and BH4 deficiency, impaired turnover of dopamine and serotonin, thus developing severe neurological deterioration unless treated early with substitutive therapy (BH4, L-dopa, and 5-hydroxytryptophan), complementary or alternative to a Phe-restricted diet [24]. Primapterinuria, a recently described variant of HPA proposed to be due to a defect in the phenylalanine-4-hydroxylase stimulating protein, pterin-4~-carbinolamine dehydratase, results in a mild and transient clinical course [4].…”

Section: Introductionmentioning

confidence: 99%

Differential diagnosis of hyperphenylalaninaemia by a combined phenylalanine-tetrahydrobiopterin loading test

Ponzone

Guardamagna²,

Spada³

et al. 1993

Eur J Pediatr

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We describe a new fully reliable method for the differential diagnosis of tetrahydrobiopterin-dependent hyperphenylalaninaemia (HPA). The method comprises the combined phenylalanine (Phe) plus tetrahydrobiopterin (BH4) oral loading test and enables the selective screening of BH4 deficiency when pterin analysis is not available or when a clear diagnosis has not been previously made. It should be performed together with the measurement of dihydropteridine reductase (DHPR) activity in blood. The new combined loading test was performed in nine patients with primary HPA, three with classical phenylketonuria (PKU), three with DHPR deficiency, and three with 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency. Three hours after oral Phe loading (100 mg/kg body weight), synthetic BH4 was administered orally at doses of either 7.5 or 20 mg/kg body weight. Amino acid (Phe and tyrosine) and pterin (neopterin and biopterin) metabolism and kinetics were analysed. By exploiting the decrease in serum Phe 4 and 8 h after administration, a clear response was obtained with the higher BH4 dose (20 mg/kg body weight), allowing detection of all cases of BH4 deficiency, as well as differentiation of BH4 synthesis from regeneration defects. Since DHPR deficient patients who were previously shown to be non-responsive to the simple BH4 loading test gave a positive response, the combined Phe plus BH4 loading test can be used as a more reliable tool for the differential diagnosis of HPA in these patients. Moreover, it takes advantage of being performed while patients are on a Phe-restricted diet.

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“…The characteristic pattern of pterins excreted in urine makes it possible to identify all four variants of tetrahydrobiopterin deficiency. The following enzyme defects are known to cause tetrahydrobiopterindependent hyperphenylalaninaemia: GTP cyclohydrolase I (GTPCH, McKusick 233910), 6-pyruvoyltetrahydropterin synthase (PTPS, McKusick 261640), dihydropteridine reductase (DHPR, McKusick 262630); and primapterinuria presumably due to carbinolamine dehydratase deficiency (Scriver et al 1989;Blau et al 1989).…”

mentioning

confidence: 99%