Blaskovics, M E

Blau, N

Giudici, T A

Pteridines

Blaskovics M. E.

Giudici T. A.

Blau N.

Directory of Open Access Journals

Primapterinuria: A Clinical Update

M. E. Blaskovics

T. A. Giudici

N. Blau

Crossref

ZORA

Zurich Open Repository andArchiveUniversity of ZurichMain LibraryStrickhofstrasse 39CH-8057 Zurichwww.zora.uzh.chYear: 1991Primapterinuria: A Clinical UpdateBlaskovics, M E; Giudici, T A; Blau, NDOI: https://doi.org/10.1515/pteridines.1991.3.12.33Posted at the Zurich Open Repository and Archive, University of ZurichZORA URL: https://doi.org/10.5167/uzh-154355Journal ArticlePublished VersionOriginally published at:Blaskovics, M E; Giudici, T A; Blau, N (1991). Primapterinuria: A Clinical Update. Pteridines, 3(1-2):33-34.DOI: https://doi.org/10.1515/pteridines.1991.3.12.33Blaskovics et al.: Primapterinuria: A clinical update 33 Ptcridines Voi. 3, pp. 3 3 - 3 4 Short Communication Primapterinuria: A Clinical Update M. E. Blaskovics, T. A. Giudici* and N. Blau** Kaiser Permanente Medicai Center, 9985 Sierra Avenue, Fontana, California 92335, U. S. A. * Childrens Hospital, Division of Medical Genetics, Los Angeles, California, USA ** University Children's Hospital, Zurich, Switzerland (Received March 1992) Introduction Primapterinuria is the recently discovered variant of hyperphenylalaninemia characterized by the excretion of 7-substituted pterins in the patients urine (1). Pri-mapterinuria differs from the classical PKU and other variants of tetrahydrobiopterin deficiency because these patients do not need treatment with a low-phenylalanine diet or with neurotransmitter precur-sors L-DOPA and 5-hydroxytryptophan. The first patients were described by Dhondt et al. (2) and Blaskovics & Giudici (3). A loading test with tetra-hydrobiopterin was the first indication that primap-terin (7-biopterin) may derive from 6-biopterin (4). Tetrahydrobiopterin, dihydrobiopterin and sepiap-terin given orally resulted in a significant increase in 6- and 7-substituted biopterin, and the ratio remained the same (1.0 to 1.5) after loading (5). From in vitro experiments it is known that primapterin can be formed during the phenylalanine-4-hydroxylase re-action in a pterin-4a-carbinolamine dehydratase free system (6). To the present time all known enzymes involved in the biosynthesis or regeneration of tetrah-ydrobiopterin have been found to be normal in these patients and a pterin-4a-carbinolamine dehydratase deficiency has been proposed (Fig. 1). Results and Discussion Nine patients with this new disorder in the regener-ation of tetrahydrobiopterin are now known. The infants initially present with variably elevated plasma phenylalanine (Phe) levels and are recognized in new-born screening programs. The Phe levels may rise to the 25 to 35 mg% range. If started on a low-Phe diet the Phe levels fall rapidly and Phe often needs to be quickly replaced. Phe levels gradually decrease over NADH Ψ Tetrahydrobiopterin 4a-Peroxy-tetrahydrobiopterin \l Dihydropteridine reductase NAD Phenylalanine hydroxylase 4a-Carbinolamlne-tetrahydroblopterln Tyrosine Carbinolamine# / dehydratase q-Dihydrobiopterin ^ H j O \ pt ri lamine — / atase jlL· Phenylalanine Figure 1. Phenylalanine-4-hydroxylase regenerating system and possible defect in primapterinuria. o ë E J S T S Ρ y) I 1 6 - B l o p t e r l n 7 - B l o p t e r l n ^ T H B J S TS NORMAL ( 3 » ) Figure 2. 6-Biopterin, 7-biopterin (primapterin) and tetrahy-drobiopterin (THB) in two children with primapterinuria at different ages. % T H B of the sum of all biopterins. N. B. = newborn Pteridines / Vol.3 / No. 1/2 Copyright © 1992 Walter de Gruyter • Berlin • New York 34 Blaskovics et al.·. Primapterinuria: A clinical update time to normal regardless of dietary Phe intake. Seven of the affected children are now on normal diets and Phe levels arc in the normal range; the two others are moving in that direction. These infants and children would fall into the category of transient hyperphen-ylalaninemia/phenylketonuria unless they are identi-fied by their urinary pterin profile. The only physical clinical findings of note have been transiently variable muscle tone, either hyper or hypo. In all instances, to the present time, the condition appears to be benign. All measurable substrates related to normal function-ing have been present. The known phenylalanine hy-droxylating system enzymes measured appear to be normal; however, phenylalanine-4-hydroxylase and pterin-4a-carbinolamine dehydratase, per se, have not been measured. The persisting abnormalities appear to be subnormal levels of tetrahydrobiopterin and elevated levels of primapterin (Fig. 2). It would appear that primapterin or its tetrahydro form has some effect on phenylalanine-4-hydroxylase. Acknowledgement This work was supported by Southern California Per-manente Medical Group, the California Department of Health Services Project No. 88-93525, and by the Swiss National Foundation grant No. 31-28797.90. References 1. Curtius, H. Ch., Küster, Th., Matasovic, Α., Blau, Ν. & Dhondt , J. L. (1988) Biochem. Biophys. Res. Commun. 153, 7 1 5 - 7 2 1 . 2. Dhondt , J. L., Guibaud, P., Rolland, M. O., Dorche, C., Andre, S., Forzy, G. & Hayte, J. M. (1988) Eur. J. Pediatr. 147, 1 5 3 - 1 5 7 . 3. Blaskovics, M. & Giudici, T. A. (1988) New Engl. J. Med. 319: 1611 —1612. 4. Blau, Ν., Curtius, H. Ch., Küster, Th., Matasovic, Α., Schoe-don, G. & Dhondt , J. L., Guibaud, P., Giudici, T. A. & Blaskovisc, M. (1989) J. Inher. Metab. Dis. 12 Suppl. 2, 3 3 5 - 3 3 8 . 5. Blau, Ν., Kierat, L., Curtius, H. Ch., Blaskovics, M. & Giudici, T. A. (1992) J. Inher. Metab. Dis. in press. 6. Curtius, H. Ch., Adler, C „ Rebrin, I., Heizmann, C. & Ghisla, S. (1990) Biochem. Biophys. Res. Commun. 172, 1 0 6 0 - 1 0 6 6 . Pteridines / Vol. 3 / No. 1/2 

https://www.zora.uzh.ch/id/eprint/154355/1/ZORA_NL_154355.pdf

Primapterinuria: A Clinical Update

Abstract

Similar works

Full text

Available Versions

Directory of Open Access Journals

Crossref

ZORA