Abstract
Amniocentesis was performed at 19 weeks gestation in a mother who had previously delivered a boy with “dihydrobiopterin synthetase” (DHBS) deficiency. The amniotic fluid contained neopterin in high (136 nmol/l) and biopterin in very low concentrations (1.8 nmol/l). The activity of the phosphate-eliminating enzyme (PEE, also called 6-pyruvoyl tetrahydropterin synthase, substrate: 7,8-dihydroneoptein triphosphate) which is present in liver and erythrocytes and defective in DHBS deficiency, was measured in the erythrocytes of the family members. The fetal sample showed only 2% of the activity of healthy adult controls and was comparable with that of the affected sibling. Obligate heterozygotes had activities around 20% of the controls. Two fetal control samples showed even higher activities than adult erythrocytes. Sepiapterin reductase activities were normal in all cases. At autopsy, PEE deficiency was confirmed in the liver of the fetus. We concluded that DHBS deficiency (and most probably also GTP cyclohydrolase I deficiency) can be diagnosed by metabolite measurements in amniotic fluid. PEE activity is measurable in erythrocytes, although the assay needs to be improved. Since maternal tetrahydrobiopterin does not cross the placenta, treatment of a tetrahydrobiopterin-deficient fetus with tetrahydrobiopterin in utero is not possible.
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Abbreviations
- B:
-
biopterin
- BH4 :
-
d-erythro 5,6(R),7,8-tetrahydrobiopterin
- %B:
-
100 B/(B+N)
- DHBS:
-
“dihydrobiopterin synthetase”
- HPLC:
-
high-performance liquid chromatography
- N:
-
neopterin
- PEE:
-
phosphate-eliminating enzyme=6-pyruvoyl tetrahydropterin synthase, substrate: 7,8-dihydroneopterin triphosphate
References
Giuliani R, Costa de Costa J, Dutra-Filho CS, Niederwieser A (1983) Tetrahydrobiopterin deficiency in two patients with phenylketonuria who did not respond adequately to dietary treatment. Rev Brasil Genet VI:557–564
Kaufman S, Holtzman NA, Milstien S, Butler IJ, Krumholz A (1975) Phenylketonuria due to a deficiency of dihydropteridine reductase. N Engl J Med 293:785–790
Kaufman S, Berlow S, Summer GK, Milstien S, Schulman JD, Orloff S, Spielberg S, Pueschel S (1978) Hyperphenylalanienemia due to a deficiency of biopterin. A variant form of phenylketonuria. N Engl J Med 299:673–679
Niederwieser A, Curtius Ch, Bettoni O, Bieri J, Schircks B, Viscontini M, Schaub J (1979) Atypical phenylketonuria caused by 7,8-dihydrobiopterin synthetase deficiency. Lancet I:131–133
Niederwieser A, Blau N, Wang M, Joller P, Atarés M, Cardesa-Garcia J (1984) GTP cyclohydrolase I deficiency, a new enzyme defect causing hyperphenylalaninemia with neopterin, biopterin, dopamine, and serotonin deficiencies and muscular hypotonia. Eur J Pediatr 141:208–214
Niederwieser A, Staudenmann W, Wetzel E (1984) HPLC with column switching for the analysis of biogenic amine metabolites and pterins. J Chromatogr 290:237–246
Niederwieser A, Leimbacher W, Curtius HCh, Ponzone A, Rey F, Leupold D (1985) Atypical phenylketonuria with “dihydrobiopterin synthetase” deficiency: absence of phosphate-eliminating enzyme activity demonstrated in liver. Eur J Pediatr 144:13–16
Yoshioka S, Masada M, Yoshida T, Mizokami T, Akino M, Matsuo N (1984) Atypical phenylketonuria due to biopterin deficiency: diagnosis by assay of an enzyme involved in the synthesis of sepiapterin from dihydroneopterin triphosphate. Zoolog Sci 1:74–81
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Niederwieser, A., Shintaku, H., Hasler, T. et al. Prenatal diagnosis of “dihydrobiopterin synthetase” deficiency, a variant form of phenylketonuria. Eur J Pediatr 145, 176–178 (1986). https://doi.org/10.1007/BF00446058
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DOI: https://doi.org/10.1007/BF00446058