Tyrosine Hydroxylase Deficiency Presenting with a Biphasic Clinical Course

Abstract

Tyrosine hydroxylase deficiency, a cause of the autosomal recessive form of L-DOPA responsive dystonia, has been associated with a broad spectrum of movement disorders and clinical courses. We describe a new patient presenting with an early onset spastic paraplegia who later developed a progressive generalized dystonic-dyskinetic syndrome. He markedly improved with a very low dosage of L-DOPA/carbidopa, while higher dosages were not tolerated. Two novel mutations (p.G414R/p.L510Q) were detected in the TH gene.

Hypopharyngeal paraganglioma: Case report and review of the literature

“…Correlation between residual enzyme activity and clinical severity has not been established in TH deficiency. In contrast, it appears that the concentration of HVA in CSF is indicative of phenotypic severity; HVA levels range from undetectable to 30% of the lower limit of the reference range in patients with severe phenotypes4, 7, 8, 17, 18 and from 46 to 60% in patients with intermediate phenotypes 10, 19, 20. HVA concentrations in our patients (5.2–14.5%) fell into the levels suggested for severe phenotypes of TH deficiency (Table 1).…”

“…Tyrosine hydroxylase (TH, EC 1.14.16.2) is the rate‐limiting step in the biosynthesis of catecholamines 1. TH deficiency (MIM#605407) is a rare metabolic disorder; it has been reported in ∼30 patients in the literature 2–10. Clinical manifestations derive mainly from chronic dopamine deficiency in the developing brain 9, 11.…”

“…Clinical manifestations derive mainly from chronic dopamine deficiency in the developing brain 9, 11. Patients may present with a severe clinical phenotype characterized by lack of motor development, parkinsonism, dystonia, and oculogyric crises associated with autonomic and endocrine dysfunction 2–11. Intermediate phenotypes also occur in TH deficiency and some patients may present with dopa responsive dystonia similar to Segawa disease 12.…”

The phenotypic spectrum of paediatric neurotransmitter diseases and infantile parkinsonism

“…Evidence of upper motor neuron signs is common in disorders of monoamine synthesis (Blau et al 2001a). Ataxia, dysarthria and ocular apraxia have also been reported (Giovanniello et al 2007;Lü decke et al 1996). Acquired microcephaly occurs in the severe forms of BH 4 disorders and it has also been reported in AADC deficiency (Blau et al 2001a;Swoboda et al 1999).…”

“…In the dominantly inherited form of GTPCH deficiency, cognition is intact. Patients with intermediate phenotypes may have borderline or normal cognition (Giovanniello et al 2007;Hoffmann et al 2003;Horvath et al 2008;Sedel et al 2008;Swoboda et al 1999). It is thought that the early effects of monoamine deficiency in the developing brain may account for the cognitive deficits.…”