Wernicke Encephalopathy Complicating a Distinctive POLG Phenotype With MNGIE-Like Features

Area of Science:

• Genetics
• Neurology
• Mitochondrial Diseases

Background:

• Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder.
• It is typically caused by thymidine phosphorylase (TYMP) gene variants.
• MNGIE presents with severe gastrointestinal and neurological symptoms.

Purpose of the Study:

• To investigate the genetic basis of MNGIE-like symptoms in identical twins.
• To expand the understanding of POLG-related disorders.
• To identify novel genetic variants associated with mitochondrial diseases.

Main Methods:

• Next-generation sequencing (NGS) using a custom mitochondrial gene panel.
• Analysis of compound heterozygous variants in the POLG gene.
• Quantification of mtDNA and analysis of mtDNA deletions in skeletal muscle.

Main Results:

• Identified compound heterozygous variants in the POLG gene (paternal: p.Thr251Ile and p.Pro587Leu; maternal: p.Arg853Gly).
• Observed significant mtDNA depletion in skeletal muscle.
• The phenotype showed MNGIE-like features, including gastrointestinal dysmotility and leukoencephalopathy.

Conclusions:

• The identified POLG variants represent a distinct phenotype with MNGIE-like features.
• This expands the clinical and genetic spectrum of POLG-related diseases.
• Monitoring for thiamine deficiency is crucial in mitochondrial patients with severe gastrointestinal dysmotility.