Alpers Disease is a progressive, neurodevelopmental, mitochondrial DNA depletion syndrome that begins in early childhood and is characterized by three co-occurring clinical symptoms: psychomotor regression (dementia); seizures; and liver disease.
Most individuals with Alpers’ disease do not show symptoms at birth and develop normally for weeks to years before the onset of symptoms. Symptoms include increased muscle tone with exaggerated reflexes (spasticity), seizures, and loss of cognitive ability (dementia). About 80 percent of individuals with Alpers’ disease develop symptoms in the first two years of life. The first symptoms of the disorder are usually nonspecific and may include hypoglycemia secondary to underlying liver disease, failure to thrive, infection-associated encephalopathy, spasticity, myoclonus (involuntary jerking of a muscle or group of muscles), seizures, or liver failure. An increased protein level is seen in cerebrospinal fluid analysis. Cortical blindness (loss of vision due to damage to the area of the cortex that controls vision) develops in about 25 percent of cases. Gastrointestinal dysfunction and cardiomyopathy may occur. Dementia is typically episodic and often associated with an infection that occurs while another disease is in process. Seizures may be difficult to control and unrelenting seizures can cause developmental regression as well. “Alpers-like” disorders without liver disease are genetically different and have a different clinical course.
The cause of this disease appears to be multifactorial, with genetics, metabolic factors, prion like molecules, and mitochondrial issues all playing a role in the expression of this disorder. This autosomal recessive disease is caused by mutations in the gene for the mitochondrial DNA polymerase POLG with the diagnosis established by testing for the POLG gene. The disease occurs in about one in 100,000 persons.
There is no cure for Alpers’ disease and no way to slow its progression. Treatment is symptomatic and supportive. Anticonvulsants may be used to treat the seizures, but at times the seizures do not respond well to therapy, even at high doses. Therefore, the benefit of seizure control should be weighted against what could be excessive sedation from the anticonvulsant. Valproate should not be used since it can increase the risk of liver failure. Physical therapy may help to relieve spasticity and maintain or increase muscle tone.