An international survey of patients with tetrahydrobiopterin deficiencies presenting with hyperphenylalaninaemia
- 23 June 2012
- journal article
- Published by Wiley in Journal of Inherited Metabolic Disease
- Vol. 35 (6), 963-973
- https://doi.org/10.1007/s10545-012-9506-x
Abstract
The present study summarizes clinical and biochemical findings, current treatment strategies and follow-up in patients with tetrahydrobiopterin (BH4) deficiencies. We analyzed the clinical, biochemical and treatment data of 626 patients with BH4 deficiencies [355 with 6-pyruvoyl-tetrahydropterin synthase (PTPS), 217 with dihydropteridine reductase (DHPR), 31 with autosomal recessive GTP cyclohydrolase I (GTPCH), and 23 with pterin-4a-carbinolamine dehydratase (PCD) deficiencies] from the BIODEF Database. Patients with autosomal dominant GTPCH and SR deficiencies will not be discussed in detail. Up to 57 % of neonates with BH4 deficiencies are already clinically symptomatic. During infancy and childhood, the predominant symptoms are muscular hypotonia, mental retardation and age-dependent movement disorders, including dystonia. The laboratory diagnosis of BH4 deficiency is based on a positive newborn screening (NBS) for phenylketonuria (PKU), characteristic profiles of urinary or dried blood spot pterins (biopterin, neopterin, and primapterin), and the measurement of DHPR activity in blood. Some patients with autosomal recessive GTPCH deficiency and all with sepiapterin reductase deficiency may be diagnosed late due to normal blood phenylalanine in NBS. L-dopa, 5-hydroxytryptophan, and BH4 are supplemented in PTPS and GTPCH-deficient patients, whereas L-dopa, 5-hydroxytryptophan, folinic acid and diet are used in DHPR-deficient patients. Medication doses vary widely among patients, and our understanding of the effects of dopamine agonists and monoamine catabolism inhibitors are limited. BH4 deficiencies are a group of treatable pediatric neurotransmitter disorders that are characterized by motor dysfunction, mental retardation, impaired muscle tone, movement disorders and epileptic seizures. Although the outcomes of BH4 deficiencies are highly variable, early diagnosis and treatment result in improved outcomes.This publication has 31 references indexed in Scilit:
- PhenylketonuriaThe Lancet, 2010
- Dopamine agonists in 6-pyruvoyl tetrahydropterin synthase deficiencyNeurology, 2009
- Disorders of biopterin metabolismJournal of Inherited Metabolic Disease, 2009
- Serum prolactin as a tool for the follow‐up of treated DHPR‐deficient patientsJournal of Inherited Metabolic Disease, 2008
- Long‐term outcome and neuroradiological findings of 31 patients with 6‐pyruvoyltetrahydropterin synthase deficiencyJournal of Inherited Metabolic Disease, 2006
- International database of tetrahydrobiopterin deficienciesJournal of Inherited Metabolic Disease, 1995
- Progression of 6‐pyruvoyl‐tetrahydropterin synthase deficiency from a peripheral into a central phenotypeJournal of Inherited Metabolic Disease, 1990
- Folinic acid therapy in treatment of dihydropteridine reductase deficiencyThe Journal of Pediatrics, 1987
- Clinical role of pteridine therapy in tetrahydrobiopterin deficiencyJournal of Inherited Metabolic Disease, 1985
- NEW VARIANT OF PHENYLKETONURIA WITH PROGRESSIVE NEUROLOGICAL ILLNESS UNRESPONSIVE TO PHENYLALANINE RESTRICTIONThe Lancet, 1975