Pregnancy During Nitisinone Treatment for Tyrosinaemia Type I: First Human Experience
A 19 year old woman with tyrosinaemia type 1 gave birth to a healthy girl after 41 weeks of gestation. Nitisinone was continued throughout the pregnancy (maternal levels 68–96 μmol/l, target level 30–60 μmol/l). Tyrosine levels during pregnancy were between 500 and 693 μmol/l (normal values 20–120 μmol/l) and phenylalanine levels between 8 and 39 μmol/l (normal values 30–100 μmol/l). Nitisinone was measurable in neonatal blood immediately after birth, at a level comparable to the simultaneous level in the mother. Nitisinone half-life in the neonate was estimated to be 90 h. Tyrosine levels in the neonate decreased from 1,157 μmol/l at birth (cord blood) to normal levels within 4 weeks. Phenylalanine levels in the neonate were normal from birth on. The child had a normal psychomotor development as assessed throughout the first year of life.
This is the first report worldwide of a pregnancy during treatment with nitisinone.
In this case, no adverse effects of nitisinone, maternal high tyrosine or low phenylalanine were detected in the child, so far. Long-term results in a larger cohort of pregnancies and births are needed to determine whether nitisinone can be administered safely during pregnancy.
KeywordsAmino Acid Mixture Fanconi Syndrome Autosomal Recessive Disease Fetal Plasma Phenylalanine Level
David Cassiman is a fundamental – clinical researcher for FWO-Vlaanderen.
Roland Devlieger is supported by FWO-Vlaanderen.
Karel Allegaert is supported by FWO-Vlaanderen.
- Davit-Spraul A, Rhomdame H, Poggi-Bach J (2011) Simple and fast quantification of nitisone (NTBC) using liquid chromatography tandem mass spectrometry method in plasma of tyrosinemia type 1 patients. J Chromatogr Sci (in press).Google Scholar
- Devlieger H, Martens G, Bekaert A, Eeckels R, Vlietinck R (1996) Perinatale activiteiten in Vlaanderen. 94–116 http://www.neonatologie.ugent.be/SPE-standaarden.pdf. Accessed 31 May 2011
- Mitchell GA, Grompe M, Lambert M, Tanguay RM (2001) Hypertyrosinemia, in Scriver CR, Beadudet AL, Sly WS, Valle D (eds) The Metabolic & Molecular Bases of Inherited Disease, 8th Ed, MCcGraw-Hill, New York, p 1778Google Scholar