Alpers' disease

Alpers' disease is a rare inherited disorder affecting the 'grey matter' of the brain. It causes progressive loss of developmental milestones, severe and persistent epilepsy and liver disease, usually in infants and young children.

What causes Alpers' disease?

Alpers' disease is one of a large and varied group of disorders known as mitochondrial diseases. It is a genetic condition causing biochemical abnormalities in the central nervous system, particularly the brain and the liver. The POLG gene has been found to have some mutations associated with the features of the disease but, as yet, it is very often not possible to detect the exact genetic fault with which to confirm the diagnosis.

How is Alpers' disease diagnosed?

Alpers' disease may be suspected from your child’s symptoms together with an electroencephalogram (EEG) which often shows a distinctive brain-wave pattern. In the later stages of the disease, examining a piece of liver (biopsy) may be helpful and a blood test looking for the POLG mutation may confirm the diagnosis. A negative test, however, does not exclude it.

Does Alpers' disease have an alternative name?

The condition was first described in 1931 by Dr Alpers. It is possible that more than one disease was originally categorised as Alpers' disease so, to be more specific, the term progressive neuronal degeneration of childhood with liver disease (PNDC) also came to be used, as well as progressive sclerosing poliodystrophy and progressive infantile poliodystrophy. If genetically confirmed, it can be called POLG disease.

Is Alpers' disease inherited?

Alpers' disease is an autosomal recessive disorder. This means that both parents are carriers of the disease. Human beings have about 30 to 40,000 different genes, each of which has a function in making an individual person. The genes are arranged in pairs (one of the pair from each parent) on 23 chromosomes.

Inevitably, some of these genes are faulty. A normal gene can overcome a faulty one, but if both genes in the pair are faulty, the genetic instructions cannot work. Most people carry different faulty genes but in Alpers' disease (and other recessive conditions) parents, though healthy themselves, carry the same faulty genes, and risk passing them on to their children. Each pregnancy carries a 25 per cent chance of the child being affected.

Is prenatal testing available?

At present there is no way of telling if an unborn baby will be affected.

How common is Alpers' disease?

Due to the difficulty in confirming the diagnosis it is not possible to be certain but it is likely to be approximately 1:100,000.

How does Alpers' disease progress?

Your child may or may not have shown some developmental delay prior to the onset of the main disease symptoms, which usually occur within the first few years of life. These may initially involve a loss of previously learnt skills and/or a sudden onset of seizures which are usually very difficult to control.

The combination of the severe epilepsy and the ongoing brain disease, which is causing the seizures, leads to increasing loss of skills and awareness. The infant often develops some physical stiffness (spasticity) and subtle involuntary movements especially of hands, feet, face and head. The optic nerve may be affected leading to loss of vision.

Ultimately the seizures become almost continuous (epilepsy partialis continua). Though upsetting to witness, they appear not to be unduly distressing to the child who is likely to be unaware of what is happening. Parents and carers will be aware of the child’s increasing frailty, and death is usually relatively peaceful and expected when the time comes. The course of the disease is usually rapid and eventually the combination of the diseased brain and increasing physical weakness becomes too great to sustain life, and death usually occurs within a year.

Very rarely older children and teenagers may develop an apparently similar condition called juvenile Alpers’ disease, whose course may be more protracted, over very many years.

Is there any treatment?

Although there is no treatment yet available that can stop the disease, every effort is made to treat the symptoms. Drugs are given to try to reduce some of the seizures, though it will be impossible to control them completely so the aim will be to treat the main convulsions without necessarily over-medicating and causing unwanted side-effects. Treatment for infections and to relieve any muscle spasm as well as pain relief and sedative drugs can be given if required and feeding can be assisted. Physiotherapists and others can advise parents on positioning, seating and exercising the limbs to maintain comfort.

Is any research being done?

Research is progressing in various areas concerning progressive neurological diseases, particularly mitochondrial disorders, and genetics. Sadly, however, any treatment that could stop or reverse the disease process is unlikely to be discovered quickly enough to help children already affected. Your child’s neurologist and information available from the support group can keep you informed of research progress.

Compiled by: 
The Neurology Liaison Nurse Specialist in collaboration with the Child and Family Information Group
Last review date: 
May 2013