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Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes
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Mitochondrial neurogastrointestinal encephalomyopathy in three siblings: clinical, genetic and neuroradiological

W M M Schüpbach1, K Madhavi Vadday, A Schaller

  • 1Department of Neurology, University Hospital-Inselspital, 3010 Bern, Switzerland.

Journal of Neurology
|February 13, 2007
PubMed

Insights

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder. This study identifies a new mutation and shows urinary thymidine is detectable in carriers, offering new diagnostic insights.

Area of Science:

  • Genetics and rare diseases
  • Neuroscience
  • Mitochondrial biology

Background:

  • Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder caused by thymidine phosphorylase (TP) gene mutations.
  • It leads to mitochondrial dysfunction and severe multi-systemic symptoms including gastrointestinal dysmotility, cachexia, and neurological deficits.

Observation:

  • This study details three brothers with MNGIE, including monozygous twins, examining their clinical, genetic, and neuroradiological features.
  • All affected individuals exhibited gastrointestinal dysmotility, cachexia, ophthalmoplegia, muscular atrophy, and polyneuropathy.
  • Brain MRI revealed leukoencephalopathy in patients, while cognitive functions remained normal.

Findings:

  • A novel mutation (T92N) in the TP gene was identified in the affected individuals.
  • Elevated urinary thymidine levels correlated with disease severity in patients and were also detected in a heterozygous carrier, a novel finding.
  • Brain MRS showed reduced N-acetylaspartate and choline in affected areas, indicating neuronal and glial cell loss.

Implications:

  • The detection of urinary thymidine in heterozygous carriers provides a potential biomarker for MNGIE.
  • MRS findings suggest significant neuronal and axonal loss in MNGIE patients, aiding in understanding disease progression.
  • This research contributes to the diagnosis and understanding of MNGIE's complex pathophysiology.

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