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Alpers syndrome

MIM.203700

Sunday 19 June 2005

Definition: Alpers syndrome is usually characterized by a clinical triad of psychomotor retardation, intractable epilepsy, and liver failure in infants and young children.

The illness usually begins in early life with convulsions. A progressive neurologic disorder characterized by spasticity, myoclonus, and dementia ensues. Status epilepticus is often the terminating development. Definitive diagnosis is shown by postmortem examination of the brain and liver.

Alpers syndrome can be caused by mutation in the nuclear gene encoding mitochondrial DNA polymerase gamma (POLG) (MIM.174763).

Synopsis

- failure to thrive
- visual disturbances
- loss of vision
- cortical blindness
- abnormal visual evoked potential (VEP)

- liver disease

- vomiting
- developmental delay
- psychomotor regression, episodic, often associated with common - childhood infections
- hypotonia
- hypertonia
- ataxia
- seizures, sudden-onset, drug-resistant
- status epilepticus
- epilepsia partialis continua
- myoclonus
- paralysis
- dementia
- cerebral cortical neurodegeneration
- cerebellar atrophy
- neuronal loss
- sstrocytosis
- gliosis
- pseudolaminar spongiform changes
- EEG shows slow frequency high amplitude waves with high frequency polyspikes

- Onset in infancy after normal birth and neonatal period
- Rapidly progressive
- Death usually by age 3 years
- Later onset (late childhood to young adult) has been reported
- Increased sensitivity to valproic acid toxicity

Biology

- Elevated liver function tests
- Increased CSF protein
- Decreased DNA polymerase-gamma (POLG, 174763) activity
- Decreased respiratory chain complex activity

- reversible valproate hepatotoxicity due to mutations in mitochondrial DNA polymerase gamma (POLG1) (18208989)

Etiology

- germline mutations in mitochondrial polymerase gamma (POLG)

References

- Alpers syndrome presenting with anatomopathological features of fulminant autoimmune hepatitis. Witters P, Pirenne J, Aerts R, Monbaliu D, Nevens F, Verslype C, Laleman W, Roskams T, Desmet L, Vlasselaers D, MariĆ«n P, Hoffman I, Lombaerts R, Goethals E, Jaeken J, Meersseman W, Cassiman D. J Inherit Metab Dis. 2010 Aug;33(4):451. PMID: 20582478