Alpers disease is a severe and progressive neurological disorder that primarily affects children. This rare condition impacts the brain and liver, leading to a decline in neurological function and serious liver complications. Understanding Alpers disease involves recognizing its genetic origins, the range of symptoms it presents, and the approaches used for its diagnosis and management.
Defining Alpers Disease
Alpers disease, also known as Alpers-Huttenlocher syndrome, is a progressive neurodevelopmental syndrome. It is classified as a mitochondrial disease, meaning it affects the mitochondria, which are the energy-producing structures within cells. The disorder primarily impacts organs with high energy demands, such as the brain and liver. It is a rare condition, estimated to affect about 1 in 100,000 people. Symptoms typically appear in infancy or early childhood, and over time, the condition worsens, leading to increasing neurological decline and liver dysfunction.
Genetic Basis
Alpers disease is caused by mutations in the POLG gene. This gene provides instructions for making an enzyme called polymerase gamma (pol γ), which is involved in replicating and repairing mitochondrial DNA (mtDNA). Mutations in POLG impair the function of this enzyme, leading to a reduction in the amount of mtDNA or an accumulation of mutations within it. This mitochondrial DNA depletion results in decreased cellular energy, particularly affecting cells in the brain and liver that require substantial energy.
The inheritance pattern for Alpers disease is autosomal recessive. This means that an individual must inherit two copies of the mutated POLG gene, one from each parent, to develop the condition. Parents who carry one copy of the mutated gene typically do not show symptoms themselves.
Recognizing Symptoms
Symptoms of Alpers disease often emerge in early childhood, with about 80% of individuals developing symptoms before the age of two. The disease typically presents with a triad of symptoms: seizures, developmental regression, and liver dysfunction. Seizures are a common early symptom and can be difficult to control.
Developmental regression involves a loss of previously acquired skills, such as motor abilities or cognitive functions. Affected individuals may also experience spasticity, which is increased muscle tone and stiffness. Liver disease can range from elevated liver enzymes to full liver failure. Other symptoms may include vision loss, involuntary muscle jerking (myoclonus), and a general failure to thrive.
Diagnosis and Management
Diagnosis involves a clinical evaluation and specialized tests. Healthcare providers often consider the condition when a child presents with seizures, liver disease, and psychomotor regression. Genetic testing for mutations in the POLG gene can confirm the diagnosis.
Other diagnostic tools include magnetic resonance imaging (MRI) of the brain, which may show changes in gray matter, and electroencephalography (EEG), which measures brain activity. Liver biopsies may also be performed to assess liver damage. There is currently no cure for Alpers disease, and treatment focuses on managing symptoms to improve comfort and quality of life.
Anti-seizure medications are used to control seizures, though some seizures may be resistant to treatment. Physical therapy can help with spasticity and maintain muscle tone. Nutritional support, often through feeding tubes, may be necessary to ensure adequate intake. A medication called valproate is generally avoided for seizure control in Alpers disease due to its potential to worsen liver function.
Prognosis and Support
Alpers disease is a severe condition with a generally poor prognosis. Most individuals do not live past their first decade, with many surviving less than four years after symptoms begin. Common causes of death include liver failure and complications from intractable seizures.
Palliative and supportive care are integral to improving the quality of life for affected individuals. This care focuses on symptom management, pain relief, and comfort. Families can find support through patient advocacy groups and specialized medical centers.