December 24, 2010
Dear Mayo Clinic:
My son was diagnosed with Alpers' disease. What are the causes and how is it diagnosed?
Alpers' disease — now called Alpers' syndrome — is a rare and serious genetic disorder that was first described in the medical literature in 1931 by Dr. Bernard Alpers. The disease is characterized by a breakdown of the brain's grey matter, persistent seizures and liver failure. A definitive diagnosis of Alpers' syndrome can be made using a blood test to detect the gene mutation responsible for this disease.
In almost all cases of Alpers' syndrome, a genetically determined mutation of polymerase gamma 1 causes the disorder. Polymerase gamma 1 controls the development of mitochondria — cell structures that are the main source of energy for most of the body's cells. Mitochondria are particularly important for maintaining healthy brain tissue.
When the gene mutation that leads to Alpers' syndrome is present in polymerase gamma 1, the result is a decrease in mitochondrial DNA. That, in turn, leads to progressive degeneration of the brain's cerebral cortex (grey matter which covers the upper portion of the brain or cerebrum), and the basal ganglia (clusters of brain cells deep within the two cerebral hemispheres). Although uncommon, mutations in other mitochondrial genes may also be responsible for Alpers' syndrome, but the resulting symptoms are the same.
Most children with Alpers' syndrome begin having symptoms early in life, often before age 5, and the disease progresses quickly. The first symptom is usually seizures. As the disease progresses, in severe cases, seizures may become almost continuous, with some children experiencing hundreds of seizures in one day. Other symptoms may include developmental delays, dementia (loss of previously acquired cognitive skills), stiffness of the limbs, and liver problems such as cirrhosis or jaundice that eventually lead to liver failure.
The possibility of Alpers' syndrome should be investigated in children who experience both seizures and liver problems. In addition to physical and neurologic examinations, a brain MRI can be used to reveal grey matter degeneration and thus aid in diagnosis. If a blood test detects the Alpers' syndrome gene mutation, other diagnostic studies are unnecessary.
Alpers' syndrome is inherited as an autosomal recessive, meaning both of the affected child's parents are carriers of the abnormal gene and, on average, one in four of their offspring will have the condition. Because it's a genetic disorder, if Alpers' syndrome is diagnosed or suspected, a geneticist should be involved in a child's care team to help manage that aspect of the disease.
Unfortunately, no cure currently exists for Alpers' syndrome, and there's no known way to slow its progression. The goal of treatment is to ease symptoms. In some cases, anticonvulsant medications can help reduce seizures. Medications may also be helpful in decreasing complications of liver failure, although a liver transplant usually isn't an option for children with Alpers'.
Advances in the early diagnosis and treatment of Alpers' syndrome, as well as a better understanding of its causes, may eventually improve the outlook for people who have this disorder. There's a great deal of research currently investigating mitochondrial diseases. New insights into these disorders may potentially benefit children who have conditions affecting the mitochondria, including Alpers' syndrome.
— Marc Patterson, M.D., Child and Adolescent Neurology, Mayo Clinic, Rochester, Minn.