Choreatic movement disorder due to tyrosine hydroxylase deficiency caused by a novel mutation in the TH gene

Introduction: Tyrosin hydroxylase (TH) catalyzes the synthesis of L-Dopa and plays a significant role in synthesis of dopamine. The responsible gene is located on chromosome 11 p. 15.5. TH deficiency (THD) is inherited in an autosomal recessive manner. THD has a broad phenotypic spectrum, but two main types can be defined:

1. Severe neonatal course with encephalopathy

2. Progressive parkinsonism with dystonia.

Case report: Three-month-old male with progressive choreatic movements, beginning shortly after awakening, not noticeable during sleep. Developmental and weight stagnation. Due to involvement of the tongue and throat musculature oral feeding was not possible in course of the disease.

Diagnostics: Exclusion of infectious and endocrinologic causes. cMRI normal.

Metabolic diagnostics: neurotransmitter (CSF): significant reduced HVA level (68 nmol/L ref. 427 to 989 nmol/L), normal concentration of 5-HIAA, 5MTHF, and pterins. Normal DHPR-enzyme activity, phenylalanine (plasma) normal.

Molecular genetics: Mutation p.R233 H (c.698G>A) in exon 6, sequence variation p.Y274* (c.822C>A) in exon 8 (presumably functional mutation) of the TH gene.

Therapy: L-Dopa/carbidopa (4:1) was administered orally (4 mg/kg BW/day) leading to significant clinical improvement (video documented) and an ending of the movement storms, followed by normal feeding habits and progress in general development.

Conclusion: Untypical presentation of a THD proven to be caused by a new mutation manifesting as a choreatic movement storm in early infancy instead of the typical hypokinetic rigidity. Significant clinical improvement was documented under oral L-Dopa/carbidopa therapy.

In case of untypical movement disorders analysis of neurotransmitters should be considered since early diagnosis may lead to significant improvement of clinical symptoms and eventually to a better prognosis.