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Myocerebrohepatopathy spectrum disorder due to POLG mutations: A clinicopathological report

Hesham Montassir1, Yoshihiro Maegaki2, Kei Murayama3

  • 1Division of Child Neurology, Faculty of Medicine, Tottori University, Yonago, Japan; Department of Family Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt.

Brain & Development
|December 4, 2014
PubMed

Insights

This study details a Japanese infant with myocerebrohepatopathy spectrum disorder caused by POLG mutations. The case highlights severe multi-organ dysfunction and specific brain lesions in mitochondrial DNA depletion disorders.

Area of Science:

  • Genetics
  • Neurology
  • Hepatology

Background:

  • Mitochondrial DNA depletion disorders (MDDs) are a group of severe genetic conditions.
  • Mutations in the polymerase gamma (POLG) gene are a common cause of MDDs.
  • Myocerebrohepatopathy spectrum (MCHS) disorder is a severe form of MDD affecting multiple organs.

Observation:

  • A Japanese infant presented with failure to thrive, vomiting, hypotonia, and hepatomegaly.
  • Laboratory findings included hepatocellular dysfunction and elevated cerebrospinal fluid protein and lactate.
  • The infant experienced rapid deterioration and died at 8 months of age.

Findings:

  • Autopsy revealed liver fatty degeneration and fibrosis, with spongy changes and demyelination in the brain.
  • Reduced mitochondrial DNA copy number and impaired respiratory chain enzyme activity were observed in the liver.
  • Genetic analysis identified compound heterozygous POLG mutations (I1185T/A957V).

Implications:

  • This case underscores the variable organ involvement and distinct neuropathological features in POLG-related MCHS.
  • Understanding these specific patterns is crucial for diagnosing and managing mitochondrial DNA depletion disorders.
  • Further research into genotype-phenotype correlations in POLG mutations is warranted.

Keywords:
Alpers syndromeMitochondrial DNA depletionMyocerebrohepatopathy spectrum disorderPOLG

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