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Tyrosine hydroxylase deficiency with severe clinical course.

Authors :
Zafeiriou DI
Willemsen MA
Verbeek MM
Vargiami E
Ververi A
Wevers R
Source :
Molecular genetics and metabolism [Mol Genet Metab] 2009 May; Vol. 97 (1), pp. 18-20. Date of Electronic Publication: 2009 Feb 10.
Publication Year :
2009

Abstract

Tyrosine hydroxylase (TH) deficiency is a rare autosomal recessive disorder mapped to chromosome 11p15.5. Its clinical expression varies with presentations as dopa-responsive dystonia (recessive Segawa's disease), dopa-responsive infantile parkinsonism, dopa-responsive spastic paraplegia, progressive infantile encephalopathy or dopa-non-responsive dystonia. We describe a 7-year-old boy with progressive infantile encephalopathy and non-responsiveness to dopamine. The patient demonstrated generalized hypotonia, pyramidal tract dysfunction and temperature instability after the second month of life. Dystonia, tremor and oculogyric crises complicated the clinical picture during the following months. Neurotransmitter analysis in CSF disclosed almost undetectable levels of HVA and MHPG, whereas serum prolactin was profoundly increased. Subsequent molecular analysis revealed homozygosity for a missense mutation (c.707T>C) in the TH gene. l-Dopa therapy in both high and low doses resulted in massive hyperkinesias, while substitution with selegiline exerted only a mild beneficial effect. Today, at the age of 7 years, the patient demonstrates severe developmental retardation with marked trunkal hypotonia, hypokinesia and occasionally dystonic and/or hyperkinetic crises. He is the third Greek patient with TH deficiency to be reported. Since all three patients carry the same pathogenetic mutation, a founder effect is suspected.

Details

Language :
English
ISSN :
1096-7206
Volume :
97
Issue :
1
Database :
MEDLINE
Journal :
Molecular genetics and metabolism
Publication Type :
Academic Journal
Accession number :
19282209
Full Text :
https://doi.org/10.1016/j.ymgme.2009.02.001