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Alpers syndrome with prominent white matter changes
Xinhua Bao1, Ye Wu, Lee-Jun C Wong
1Department of Pediatrics, Peking University First Hospital, Beijing, China. zwhang@pku.edu.cn
Brain & Development
|October 10, 2007
Summary
Alpers syndrome, a severe neurogenetic disorder, is linked to POLG1 gene mutations. This study identifies two new POLG1 variants in a child with Alpers syndrome, highlighting potential treatment challenges.
Area of Science:
- Neurogenetics
- Mitochondrial Biology
- Neuropathology
Background:
- Alpers syndrome is a fatal neurogenetic disorder linked to mutations in the POLG1 gene, which encodes mitochondrial DNA polymerase gamma (polgamma).
- POLG1 mutations disrupt mitochondrial DNA replication and maintenance, leading to progressive neurodegeneration and organ failure.
Observation:
- A 10-year-old Chinese girl presented with refractory seizures, acute liver failure post-valproic acid exposure, cortical blindness, and psychomotor regression.
- Brain MRI revealed significant white matter changes, and cerebrospinal fluid (CSF) analysis showed increased immunological factors.
Findings:
- Two novel missense variants in the POLG1 gene, c.248T > C (p.L83P) and c.2662G > A (p.G888S), were identified in the patient.
- Neuropathological examination of the occipital lobe demonstrated neuronal loss, spongiform changes, astrocytosis, and demyelination.
Implications:
- These findings expand the spectrum of known POLG1 mutations associated with Alpers syndrome.
- The case underscores the critical role of POLG1 in mitochondrial function and neurological health.
- Understanding these genetic variants is crucial for accurate diagnosis and potential therapeutic strategies for Alpers syndrome.
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