Objective: To discuss a case of tyrosine hydroxylase deficiency presenting with resolution of symptoms on levodopa except for a dynamic segmental dystonia

Background: Dopa-responsive dystonia (DRD) has largely been associated with autosomal dominant mutations in the GCH1 gene leading to GTP cyclohydrolase 1 deficiency (1). More recently, a deficiency in tyrosine hydroxylase (TH) has been recognized to cause DRD. This is a rare disorder resulting from a genetic mutation in the TH gene on chromosome 11 (2). The phenotype ranges from DRD with complete resolution on levodopa to infantile parkinsonism and encephalopathy only partially responsive to levodopa (2).

Methods: We report a man with an usual presentation of dystonia. He grew up in rural Myanmar with limited medical care. Childhood was normal except for episodic illness with difficulty moving and speaking. At 18 years he developed difficulty writing. At 21 years he could not speak, walk, or write and was taken to a city hospital. Multiple medications were tried without benefit until carbidopa/levodopa, to which he had a miraculous response. Since then he has attempted to come off medication, however his symptoms return after several weeks. On presentation to us at 31 years he was taking 450mg levodopa/day and 4mg trihexyphenidyl/day. He had a dynamic dystonia in his neck and trunk, subtle at rest and prominent with walking. He exhibited a sensory trick when touching his hand to chin; improvement occurred to a lesser degree when he imagined this, and to an even lesser degree when the examiner touched his chin. He had no parkinsonism

Results: He underwent genetic testing, revealing a homozygous variant mutation in the TH gene (p.Thr494Met) leading to a diagnosis of autosomal recessive tyrosine hydroxylase deficiency

Conclusions: TH deficiency can cause a broad range of clinical symptoms and severity. As more cases are discovered, the phenotype expands. Here we describe a unique case of TH deficiency DRD that does not show complete response to levodopa with residual symptoms behaving like an idiopathic segmental dystonia which is task specific and responds to a sensory trick. In addition, while the history is limited, it is possible he may have had childhood episodes similar to “lethargy-irritability crises” seen in more severe cases. As more TH deficiency cases are discovered it is important to clearly identify distinguishing features to allow for proper diagnosis and treatment

References:

1. Furukawa Y, Kish S. Tyrosine Hydroxylase Deficiency. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al., editors. GeneReviews(R). Seattle (WA)1993
2. Willemsen MA, Verbeek MM, Kamsteeg EJ, de Rijk-van Andel JF, Aeby A, Blau N, et al. Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis. Brain. 2010;133(Pt 6):1810-22.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/an-unusual-presentation-of-tyrosine-hydroxylase-deficiency/