TBK1-associated motor neuron disease with concomitant vacuolar myopathy: a case resembling a multisystem proteinopathy

Abstract

We present a 75-year-old patient with an amyotrophic lateral sclerosis (ALS)-myopathy overlap phenotype and a pathogenic variant in TBK1. The ALS-myopathy overlap phenotype was extensively documented clinically, with mixed myopathic and neurogenic findings on needle EMG, muscle MRI and muscle biopsies, with presence of rimmed vacuoles immunoreactive for P62 in particular. A concomitant presentation of motor neuron disease (MND) and myopathy is most notably associated with a very rare, inherited group of diseases, known as multisystem proteinopathies (MSPs). An increasing number of genes have already been linked to an MSP phenotype, of which VCP-related MSP is the most frequent. In this report we expand the spectrum of clinical presentations of TBK1-associated disease and describe pathophysiological similarities between TBK1- and VCP-related disease.