Journal of Inherited Metabolic Disease

, Volume 41, Issue 5, pp 849–863 | Cite as

Pregnancy management and outcome in patients with four different tetrahydrobiopterin disorders

  • O. Kuseyri
  • A. Weissbach
  • N. Bruggemann
  • C. Klein
  • M. Giżewska
  • D. Karall
  • S. Scholl-Bürgi
  • H. Romanowska
  • E. Krzywińska-Zdeb
  • A. A. Monavari
  • I. Knerr
  • Z. Yapıcı
  • V. Leuzzi
  • T. Opladen
Original Article



Inborn errors of tetrahydrobiopterin (BH4) biosynthesis or recycling are a group of very rare neurometabolic diseases. Following growing awareness and improved availability of drug treatment the number of patients with BH4 disorders reaching adulthood is constantly increasing. Pregnancy care of patients with these disorders is therefore a new challenge for clinicians.


This retrospective study summarises for the first time clinical and biochemical monitoring data of 16 pregnancies in seven women with different disorders of BH4 metabolism and evaluates treatment regimens before and during pregnancy in relation to the obstetrical outcome and paediatric follow-up.


Worsening of pre-existing neurological symptoms or occurrence of new symptoms during pregnancy was not observed in most of the cases. Treatment regimens remained mostly unchanged. Pregnancies were not complicated by disease-specific features. Organ abnormalities, miscarriage, prematurity, IUGR and chromosomal changes were occasionally reported, without showing any association with the standard drug treatment for BH4 deficiencies.


Although our data on 16 pregnancies in seven patients did not present any association of standard drug treatment with an increased rate of pregnancy complications, abnormal obstetrical or paediatric outcome, an intensive clinical and biochemical supervision by a multidisciplinary team before, during and after the pregnancy in any BH4 deficiency is essential since available data on pregnancies in patients with BH4 deficiencies is limited.



5-Hydroxyindolacetic acid






5-Methyltetrahydrofolic acid




6-Pyruvoyl-tetrahydrobiopterin synthase


6-Pyruvoyl-tetrahydrobiopterin synthase deficiency


Atrial septal defect


Autosomal dominant guanosine triphosphate cyclohydrolase 1


Autosomal dominant guanosine triphosphate cyclohydrolase 1 deficiency


Autosomal recessive guanosine triphosphate cyclohydrolase 1


Autosomal recessive guanosine triphosphate cyclohydrolase 1 deficiency


Cerebral spinal fluid


Central nervous system


Dihydropteridine reductase


Dihydropteridine reductase deficiency


Dried blood spot


Gestational age


Gestational week


Homovanillic acid




International Working Group on Neurotransmitter Related Disorders


Intrauterine growth restriction




Lower segment caesarean section


Maternal phenylketonuria


Maternal PKU syndrome


Newborn screening


Nitric oxide synthase


Parkinson’s disease








Pterin-4 alpha-carbinolamine dehydratase


Sepiapterin reductase


Sepiapterin reductase deficiency




Tyrosine hydroxylase


Tryptophan hydroxylase



We thank Dr. D. Hübschmann and Dr N. Ishaque for fruitful discussion. This study was partially supported by Dietmar Hopp Stiftung, St. Leon-Rot, Germany.


No funding was provided for this work.

Compliance with ethical standards

Conflict of interest

O. Kuseyri, A. Weissbach, N. Bruggemann, C. Klein, M. Giżewska, D. Karall, S. Scholl-Bürgi, H. Romanowska, E. Krzywińska-Zdeb, A.A. Monavari, I. Knerr, Z. Yapıcı, V. Leuzzi, and T. Opladen declare that they have no conflict of interest.

Studies with animal

This article does not contain any studies with animal subjects performed by the any of the authors.

Supplementary material

10545_2018_169_MOESM1_ESM.docx (31 kb)
ESM 1 (DOCX 31 kb)


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Copyright information

© SSIEM 2018

Authors and Affiliations

  • O. Kuseyri
    • 1
  • A. Weissbach
    • 2
    • 3
  • N. Bruggemann
    • 2
    • 3
  • C. Klein
    • 2
    • 3
  • M. Giżewska
    • 4
  • D. Karall
    • 5
  • S. Scholl-Bürgi
    • 5
  • H. Romanowska
    • 4
  • E. Krzywińska-Zdeb
    • 4
  • A. A. Monavari
    • 6
  • I. Knerr
    • 6
  • Z. Yapıcı
    • 7
  • V. Leuzzi
    • 8
  • T. Opladen
    • 1
  1. 1.Division of Child Neurology and Metabolic DiseasesUniversity Children‘s Hospital HeidelbergHeidelbergGermany
  2. 2.Institute of NeurogeneticsUniversity of LübeckLübeckGermany
  3. 3.Department of NeurologyUniversity of LübeckLübeckGermany
  4. 4.Department of Paediatrics, Endocrinology, Diabetology, Metabolic Diseases and CardiologyPomeranian Medical University in SzczecinSzczecinPoland
  5. 5.Department of Paediatrics I, Inherited Metabolic DisordersMedical University of InnsbruckInnsbruckAustria
  6. 6.National Centre for Inherited Metabolic DisordersTemple Street Children’s University HospitalDublinIreland
  7. 7.Department of Child Neurology, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey
  8. 8.Department of Paediatrics and Child Neurology and PsychiatrySapienza Università di RomaRomaItaly

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