Pregnancy management and outcome in patients with four different tetrahydrobiopterin disorders
- 51 Downloads
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.
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 deficiency
Dried blood spot
International Working Group on Neurotransmitter Related Disorders
Intrauterine growth restriction
Lower segment caesarean section
Maternal PKU syndrome
Nitric oxide synthase
Pterin-4 alpha-carbinolamine dehydratase
Sepiapterin reductase deficiency
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.
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.
- Blau N, Thöny B, Cotton R, Hyland K (2001) Disorders of tetrahydrobiopterin and related biogenic amines. McGraw-Hill, New YorkGoogle Scholar
- Blau N, van Spronsen FJ (2014) Disorders of phenylalanine and tetrahydrobiopterin metabolism. In: Blau N, Duran M, Dionisi-vici C (eds) Physician's guide to the diagnosis, treatment, and follow-up of inherited metabolic diseases. Springer, Heidelberg, pp 3–21Google Scholar
- Dhondt J-L (2006) Follow-up and outcome of tetrahydrobiopterin deficiencies. In Blau, N PKU and BH4: advances in phenylketonuria and tetrahydrobiopterin. Heilbronn, SPS Verlagsgesellschaft, pp 652–677Google Scholar
- Felix JF, de Jong EM, Torfs CP, de Klein A, Rottier RJ, Tibboel D (2009) Genetic and environmental factors in the etiology of esophageal atresia and/or tracheoesophageal fistula: an overview of the current concepts. Birth Defects Research Part A: Clin Molec Teratol 85(9):747–754CrossRefGoogle Scholar
- Jacquemard F, Palaric JC, Allain H, Giraud JR (1990) Parkinson disease and pregnancy. Apropos of a case. J Gynecol Obstet Biol Reprod (Paris) 19(4):461–463Google Scholar
- Neilson JP, Gyte GM, Hickey M, Vazquez JC, Dou L (2013) Medical treatments for incomplete miscarriage. Cochrane Database Syst Rev 3:CD007223Google Scholar
- Ponzone A, Ferraris S, Baglieri S,Spada M (2006) Treatment of tetrahydrobiopterin deficiencies. In Blau, N PKU and BH4: advances in phenylketonuria and tetrahydrobiopterin. Heilbronn, SPS Verlagsgesellschaft, pp 612–637Google Scholar
- Routiot T, Lurel S, Denis E, Barbarino-Monnier P (2000) Parkinson's disease and pregnancy: case report and literature review. J Gynecol Obstet Biol Reprod (Paris) 29(5):454–457Google Scholar
- Shintaku H, Ohwada M (2013) Long-term follow-up of tetrahydrobiopterin therapy in patients with tetrahydrobiopterin deficiency in Japan. Brain Develop 35(5):406–410Google Scholar