A novel DHTKD1 gene mutation with ALS like presentation: a case report

Abstract

DHTKD1 is a nuclear gene that encodes “dehydrogenase E1 and transketolase domain-containing 1”, essential in mitochondrial metabolism. First identified in the patients of 2-amino-apidic and 2 oxoapidic aciduria, mutation in this gene has recently been implicated in CMT2Q and ALS. Here we report the case of a septuagenarian who presented with a 2 years progressive history of respiratory and neck muscle weakness without significant bulbar and limb involvement. Clinical and electrophysiological examination revealed lower motor neuron involvement with widespread chronic denervation and reinnervation. Clinical exome sequencing revealed a heterozygous nonsense variant in exon 8 of the DHTKD1 gene, which was previously described in CMT2Q. This report highlights the pleotropic phenotypic presentation of DHTKD1 mutation and the need for genetic testing even in sporadic cases of ALS presenting at a later age.

Keywords:

• DHTKD1
• ALS
• CMT2Q
• ALS genotypes

Declaration of interest

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

Figure 1. Wasting of small muscles of hand and legs. (a) Wasting of the first dorsal interossei. (b) Atrophy of the thenar and hypothenar eminences. (c) Thinning of legs. (d) Atrophy of the intrinsic foot muscles.