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

Area of Science:

• Biochemistry
• Genetics
• Neuroscience

Background:

• The DHTKD1 gene encodes a key enzyme in mitochondrial metabolism.
• Mutations in DHTKD1 have been linked to 2-amino-apidic and 2-oxo-apidic aciduria, CMT2Q, and ALS.
• Understanding DHTKD1's role is vital for diagnosing and treating related neurological disorders.

Observation:

• A septuagenarian patient presented with progressive respiratory and neck muscle weakness over two years.
• Clinical and electrophysiological findings indicated lower motor neuron involvement with chronic denervation and reinnervation.
• No significant bulbar or limb muscle involvement was noted initially.

Findings:

• Clinical exome sequencing identified a heterozygous nonsense variant in exon 8 of the DHTKD1 gene.
• This specific variant was previously associated with Charcot-Marie-Tooth disease type 2Q (CMT2Q).
• The findings link this DHTKD1 variant to a sporadic, late-onset Amyotrophic Lateral Sclerosis (ALS) presentation.

Implications:

• DHTKD1 mutations exhibit pleotropic phenotypic presentations, affecting different neurological systems.
• Genetic testing for DHTKD1 variants should be considered in sporadic ALS cases, especially those presenting later in life.
• This case expands the known clinical spectrum associated with DHTKD1 gene mutations.