gms | German Medical Science

Objective: The TPI1 gene encodes the enzyme triosephosphate Isomerase, which plays an important role in the glycolytic pathway. Homozygote or compound homozygote mutations of the gene may result in haemolytic anaemia, muscle weakness, hyperkinetic or dystonic movements, and immunodeficiency. Symptoms typically manifest in early childhood and affected individuals have a drastically shortened life span. Thus far, there is no published experience in patients presenting with severe generalized dystonia.

Methods: We present the case of a 22-year-old man with a compound heterozygous mutation of the TPI-1 gene (c.728G>C, c.350G>A), suffering from severe generalized dystonia. He had pallidal deep brain stimulation (DBS) at age 16 performed at another institution.

Results: Pallidal DBS (performed at another institution) led to initial improvement of symptoms with almost complete remission. At age 19, symptoms re-occurred and could not be managed by adaptation of stimulation settings. At age 22 he first presented with severe generalized dystonia, including oropharyngeal muscles. Gait was markedly impaired due to dystonic movements of the legs and trunk. The Burke-Fahn-Marsden Dystonia Rating Scale (BFM) was 86 points.

Conclusion: This is the first case of TPI1 associated dystonia treated with pallidal DBS reported so far. Further, this is one of few patients with TPI1 mutation surviving up to age 22. While our patient initially responded well to DBS, it remains unclear why disease progress occured one year after implantation, especially taking into account that there were no structural brain alterations detectable in MR imaging. The assumption of an underlying accumulation of dysfunctional protein aggregates, as suggested by Orosz et al., might give a possible explanation. This case highlights the still poorly understood role of genetic testing in DBS treatment for dystonia.