Home > D. General pathology > Genetic and developmental anomalies > Alpers syndrome
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
- fulminant hepatitis (20582478)
- liver failure
- microvesicular steatosis
- hepatocyte dropout
- micronodular cirrhosis
- abnormal bile duct architecture
- bile duct proliferation
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, Mariën P, Hoffman I, Lombaerts R, Goethals E, Jaeken J, Meersseman W, Cassiman D. J Inherit Metab Dis. 2010 Aug;33(4):451. PMID: 20582478
