What are the other Names for this Condition? (Also known as/Synonyms)

• Alpers Progressive Infantile Poliodystrophy
• Alpers’ Huttenlocher Disease
• Progressive Sclerosing Poliodystrophy

What is Alpers’ Disease? (Definition/Background Information)

• Alpers’ Disease is a neurodevelopmental genetic disorder that is characterized by the loss of grey matter in the brain (grey matter is a major component of the brain)
• It is caused by mutations in the POLG polymerase gene, which codes for the production of mitochondrial DNA
• Even though the disorder is inherited and present at the time of birth, symptoms may take weeks to years to develop. Once symptoms have arisen, they rapidly become worse
• The three primary symptoms of Alpers’ Disease are dementia, seizure disorder, and liver disease
• Currently, there is no cure for the disease and no way to slow progression of the symptoms. But through medications, some of the symptoms may be eased

Who gets Alpers’ Disease? (Age and Sex Distribution)

• Alpers’ Disease is a congenital (inherited) condition that is present from birth. Nevertheless, the symptoms of the condition may arise any period from birth to the age of 25 years
• Males and females are equally affected by Alpers’ Disease

What are the Risk Factors for Alpers’ Disease? (Predisposing Factors)

• Alpers’ Disease is a genetic disorder inherited in an autosomal recessive pattern. This means that the mutation must be inherited from both parents in order to inherit the disorder and manifest signs and symptoms of Alpers’ Disease
• If the individual only inherits one copy of the mutated gene, then they will be a carrier of the disorder, not showing any signs or symptoms of the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Alpers’ Disease? (Etiology)

• Alpers’ Disease is caused by mutations in the POLG polymerase gene. This polymerase aids in the production of mitochondrial DNA, which codes for the production of mitochondria
• Mitochondria are important for energy production in the body cells; they are the primary source of energy for the body’s cells. In particular, they are important in maintaining healthy brain tissue. When mutations are present in the POLG polymerase, there is a decrease of mitochondrial DNA
• This causes a progressive degeneration of grey matter in the brain. Seizures and liver disease are thought to be a result of the decrease in cellular energy, which is present due to the loss of mitochondria

What are the Signs and Symptoms of Alpers’ Disease?

About 80% of the individuals with Alpers’ Disease develop symptoms within the first two years of life. The other 20% may develop symptoms any period between the ages of 2 and 25 years.

Common signs and symptoms of Alpers’ Disease include:

• Memory loss, dementia
• Liver disease: Jaundice and cirrhosis (liver failure)
• Seizures
• Balance and coordination issues, involuntary twitches
• Reflex-related problems
• Hypotonia (weak muscle tone)
• Headaches
• Irritability
• Speech abnormalities

How is Alpers’ Disease Diagnosed?

A diagnosis of Alper's Disease may involve:

• A complete evaluation of medical history along with a thorough physical exam
• A family history of the disorder is very important

Some of the diagnostic tests may include:

• Evaluation of liver function will show elevation of transaminase enzymes
• Cerebrospinal fluid examination will show elevated levels of proteins and lactate
• POLG DNA testing is the gold-standard for confirming a diagnosis of Alper's Disease

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Alpers’ Disease?

Along with the three primary symptoms of Alpers’ Disease, such as dementia, seizures, and liver disease, other complications may also arise.

• Many individuals suffer from coordination and balance problems due to nerve damage in the brain
• A complete loss of movement may also occur
• Cortical blindness: Loss of vision due to damage of the brain area that controls vision

How is Alpers’ Disease Treated?

Currently, there is no treatment for Alpers’ Disease. However, medications are used to control the symptoms of the disease.

• Anticonvulsants are often used to manage seizures
• Physical therapy is also recommended to help maintain muscle tone and relieve spasticity

How can Alpers’ Disease be Prevented?

• Currently, there are no specific methods or guidelines to prevent Alpers’ Disease, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Alpers’ Disease? (Outcomes/Resolutions)

• Individuals with Alpers’ Disease may survive anywhere from a few months to more than 10 years after the first symptoms are noted
• Medication and therapy are beneficial in keeping the symptoms in check; however, these do not improve the survival rate

Additional and Relevant Useful Information for Alpers’ Disease:

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).