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Respiratory chain deficiency in Alpers syndrome
M Gauthier-Villars1, P Landrieu, V Cormier-Daire
1Department of Medical Genetics and INSERM U-393, Hôpital Necker-Enfants Malades, Paris, France.
Insights
Respiratory chain enzyme deficiency is a key factor in Alpers syndrome, a severe childhood epileptic encephalopathy. Early diagnosis is crucial, even without obvious liver issues or lactic acidosis, to guide treatment and avoid dangerous medications.
Area of Science:
- Biochemistry
- Neurology
- Pediatrics
Background:
- Alpers syndrome is a severe, early-onset progressive encephalopathy.
- It is characterized by developmental delay, intractable seizures, and liver dysfunction.
- Diagnosis often relies on clinical presentation and liver involvement.
Observation:
- This study investigated four unrelated children with epileptic encephalopathy and liver involvement diagnosed as Alpers syndrome.
- Respiratory chain enzyme deficiency was identified in the liver of all patients.
- Oxidative phosphorylation in skeletal muscle and blood/CSF lactate levels were normal in most patients.
Findings:
- Respiratory chain enzyme deficiency is a significant finding in Alpers syndrome.
- Liver involvement may present later in cases of isolated epileptic encephalopathy.
- Normal lactate levels do not exclude respiratory chain defects.
Implications:
- Consider respiratory chain deficiency in diagnosing severe childhood epileptic encephalopathy, even without clear liver or lactate abnormalities.
- Investigate liver respiratory chain function via biopsy before administering valproate in at-risk children due to potential hepatic failure.
- This approach can improve diagnostic accuracy and patient safety.
Abstract:
Alpers syndrome is a progressive encephalopathy of early onset, characterized by rapid and severe developmental delay, intractable seizures and liver involvement in a previously healthy child. Here, we report on respiratory chain enzyme deficiency in the liver of four unrelated children presenting with epileptic encephalopathy and liver involvement diagnosed as Alpers syndrome. Interestingly, oxidative phosphorylation in skeletal muscle was normal in 4/4 and blood and CSF lactate in 3/4 patients. Liver involvement had a late clinical onset in patients with previously isolated epileptic encephalopathy. Based on these observations, we suggest 1. to give consideration to respiratory chain deficiency in the diagnosis of severe epileptic encephalopathy in childhood, even when no clinical or biological evidence of liver involvement or lactic acidosis is noted, and 2. to investigate the respiratory chain in a needle biopsy of the liver in children with epileptic encephalopathy prior to valproate administration if biochemical indications for respiratory chain disease or hepatic disturbance are noted, as this drug is believed to occasionally trigger hepatic failure and fatal outcome.