Abstract | OBJECTIVES: The present study summarizes clinical and biochemical findings, current treatment strategies and follow-up in patients with tetrahydrobiopterin (BH(4)) deficiencies. METHODS: RESULTS: Up to 57 % of neonates with BH(4) 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 BH(4) 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 BH(4) 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. CONCLUSIONS: BH(4) 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 BH(4) deficiencies are highly variable, early diagnosis and treatment result in improved outcomes.
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Authors | Thomas Opladen, Georg F Hoffmann, Nenad Blau |
Journal | Journal of inherited metabolic disease
(J Inherit Metab Dis)
Vol. 35
Issue 6
Pg. 963-73
(Nov 2012)
ISSN: 1573-2665 [Electronic] United States |
PMID | 22729819
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biopterin
- Dihydropteridine Reductase
- Hydro-Lyases
- pterin-4a-carbinolamine dehydratase
- Phosphorus-Oxygen Lyases
- 6-pyruvoyltetrahydropterin synthase
- sapropterin
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Topics |
- Biopterin
(analogs & derivatives, deficiency)
- Data Collection
- Databases, Factual
- Dihydropteridine Reductase
(genetics)
- Female
- Humans
- Hydro-Lyases
(deficiency, genetics)
- Infant
- Infant, Newborn
- Internationality
- Male
- Phenylketonurias
(diagnosis, genetics, metabolism, therapy)
- Phosphorus-Oxygen Lyases
(deficiency, genetics)
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