Alpers disease is a genetic and progressive neurodevelopmental syndrome. The gene mutation responsible for Alpers disease causes dysregulation and depletion of the mitochondria in a person’s cells.

Mitochondria are energy-producing organelles, small structures inside the body’s cells. They use the nutrients in food and oxygen to create adenosine triphosphate (ATP). This compound provides cellular energy for various essential functions, such as muscle contraction and nerve impulse generation.

Mitochondria have their own genome known as mitochondrial DNA (mtDNA), which contains 37 genes necessary to produce ATP. As Alpers disease affects a person’s mtDNA, it influences ATP production and causes dysfunction in areas of the body that require a lot of energy, such as the brain, muscles, and liver.

This article discusses Alpers disease, its symptoms, causes, risk factors, diagnosis, treatment, and outlook.

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Alpers disease is a genetic and progressive neurologic mitochondrial disorder. It is rare, affecting an estimated 1 in 100,000 people.

Alpers disease has several names:

  • Alpers progressive infantile poliodystrophy
  • Alpers progressive sclerosing poliodystrophy
  • Alpers syndrome
  • Alpers-Huttenlocher syndrome
  • progressive neuronal degeneration of childhood with liver disease
  • Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis
  • diffuse cerebral degeneration in infancy
  • progressive cerebral poliodystrophy
  • poliodystrophy cerebral progressive

Does it affect a person’s life expectancy?

Alpers disease significantly shortens a person’s lifespan. Most people with this condition do not live past their first decade.

A person’s life expectancy may be fewer than 4 years after the initial appearance of symptoms. Common causes of death are liver failure and brain dysfunction (encephalopathy).

According to the National Institute of Neurological Disorders and Stroke, 80% of people with Alpers disease develop symptoms in the first 2 years of life. For 20% of people, symptoms develop between the ages of 2 and 25. The age of symptom onset is related to the genetic pattern of inheritance.

Alpers disease symptoms include:

Alpers disease is a genetic condition. A mutation in the POLG1 gene causes Alpers disease. This mutation reduces the effectiveness of polymerase gamma, an important part of mitochondrial DNA.

People can inherit Alpers disease in an autosomal recessive pattern. A person can develop an autosomal recessive condition if they inherit the mutated gene from each parent. There is also more than one type of gene mutation that can cause the disease.

There are two ways a person can inherit a POLG1 mutation that leads to Alpers disease:

  • Heterozygous: This means a person inherits two different versions of a gene, one from each parent. The symptoms usually begin in the early years of life, between 2 and 4 years of age.
  • Homozygous: This means a person inherits two of the same version of a gene, one from each parent. Symptoms are usually milder and develop later, around 17 to 24 years of age.

A person born to two people who carry the gene but do not have symptoms of the condition will have:

  • a 25% likelihood of inheriting two copies of the mutated gene and developing the condition
  • a 50% likelihood of inheriting one mutated and one unaffected gene, becoming a carrier
  • a 25% likelihood of inheriting two copies of the unaffected gene

Doctors diagnose Alpers syndrome based on a thorough clinical evaluation and various tests.

Symptoms triad

Doctors would consider Alpers disease if a person had the following three key symptoms:

  • seizures
  • liver disease
  • psychomotor regression

Seizures are often the first noticeable symptom. In the early stages, liver disease may be minimal or not yet present.

Gene sequencing

Doctors can confirm the presence of Alpers disease using polymerase gamma gene sequencing and a liver biopsy.

Additional clinical findings

Tests such as brain imaging, biopsies, and cerebrospinal fluid analysis can help doctors identify markers of Alpers disease.

Some of the signs they look for include:

  • increased protein in the cerebral spinal fluid
  • reduced mtDNA in muscles or the liver
  • cerebral volume loss
  • vision loss
  • brain activity abnormalities

Family history

If a person has a full sibling already diagnosed with Alpers disease, this indicates that both their biological parents are carriers. This means the person has a 25% chance of having Alpers disease like their sibling.

There is no cure for Alpers disease. Instead, the goal of treatment is to provide support and comfort and to reduce the impact of symptoms where possible.

Clinicians can adapt treatment to the needs of the individual and weigh the benefits against potential risks, such as how much stress some medications might put on the liver.

Alpers disease treatments may include:

  • anti-convulsant medication
  • muscle relaxants
  • pain medication
  • nutrition support
  • respiratory support
  • physical therapy

Clinical trials

Clinical trials are research studies to help medical professionals learn more about preventing and treating disease.

In the studies, participants test new treatments to see how well they work. Often, researchers assign the treatments randomly. Participants do not know whether they have received the treatment being studied or a placebo.

Clinical trial participation is voluntary. Researchers will only consider participants for a trial if they meet inclusion criteria. People interested in participating may wish to discuss it with their primary care doctor.

The National Library of Medicine maintains the website, a searchable database of studies. People can look for studies that are in progress and recruiting or find information about complete studies.

Living with Alpers disease involves symptom management and quality of life support.

Learning about the condition may help involved individuals feel more connected to the treatment plan. Reaching out for mental health support may also be of benefit.

The National Organization for Rare Disorders (NORD) has assistance programs that may help with the following:

NORD also has a directory of patient organizations included in their Programs & Resources where patients and family members can look for information and support.

Alpers disease is a progressive genetic condition. It causes mitochondrial damage and leads to dysfunction in organs that require cellular energy, such as the brain and the liver.

There is no cure for Alpers disease. Treatment is supportive and palliative and designed to make the person comfortable.