Motor neuron disease in three asymptomatic pVal50Met TTR gene carriers

Abstract

We describe three unrelated patients with sporadic motor neuron disease (MND) and hereditary amyloid transthyretin (ATTRv) amyloidosis family history, who were asymptomatic carriers of the pVal50Met mutation of transthyretin (TTR) gene. Patients 1 and 2 were a 43-year-old man with a spinal-onset of ALS and a 37-year-old woman with a bulbar-onset of ALS, who died due to respiratory complications five and two years after disease onset, respectively. Patient 3 is a 52-year-old woman, with a two-year history of a probable primary lateral sclerosis, and a frontotemporal dysfunction. Imaging, cerebrospinal fluid (CSF) and nerve conduction and small fiber tests were normal in all. Genetic testing for ALS was negative in the two patients tested. Previous studies in MND patients have identified reduced TTR levels in CSF and neuronal gene overexpression, suggesting a neuroprotective role of TTR. The association of MND in patients with TTR gene mutations has not yet been described.

Keywords:

• Amyotrophic lateral sclerosis
• motor neuron disease
• primary lateral sclerosis
• transthyretin
• TTR gene

Declaration of interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by the Brainteaser Project—Bringing Artificial Intelligence home for a better care of amyotrophic lateral sclerosis and multiple sclerosis funded by the European Union’ Horizon 2020 research and innovation program, under Grant Agreement No. GA101017598.