Alexander disease

Also known as: Alexander Leukodystrophy; AxD


Alexander disease (AxD) is an extremely rare genetic disease belonging to a group of conditions called leukodystrophies. It involves degeneration of the brain’swhite matter(nerve fibres & fatty, insulating, myelin sheaths). It is normally caused by a one-off mutation (change) in the parents’ sperm or egg, or very occasionally inherited from a mildly affected parent.


Medical text written June 2017 by Thomas E Beeby, Medical Student, Cambridge University School of Clinical Medicine; approved by Dr A P J Parker, Consultant Paediatric Neurologist, Addenbrooke’s Hospital, Cambridge, UK.

Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information is provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.

What are the symptoms?

The infantile form generally appears by age two, with features including megalencephaly (large head), developmental delay, persistent vomiting, weight loss, seizures, muscle stiffness and reduced movement. Hydrocephalus (water on the brain) may be present, sometimes picked up by antenatal ultrasound scans.

The juvenile form appears slightly later, around 3-12 years old, with trouble speaking or swallowing, possibly psychiatric problems, but rarely seizures.

The adult form is the most varied and can occur from 13-70 plus. Symptoms may appear gradually, and include difficulty eating or speaking, very early or late puberty, deterioration of cognition (reasoning, memory or attention), changes in walking pattern, palatal myoclonus (spasm of the roof of the mouth), nystagmus (uncontrolled eye movements), sleep apnoea, bowel or bladder problems, and kyphoscoliosis (curving of the spine). Some adults are misdiagnosed with Multiple Sclerosis (MS) or Alzheimer’s Disease.

What are the causes?

Symptoms are caused by failure of nerve signals in the brain. This occurs because the myelin sheaths surrounding nerve axons degenerate, disrupting electrical conduction. This is comparable to the plastic coating of electrical cables wearing down, allowing damage to the wires inside. The first step happens in astrocyte cells,which are important for supporting the normal function of neurons (nerve cells) and oligodendrocytes (which make myelin). Alexander disease is caused by a change in the GFAP gene, producing abnormal GFAP proteins, which clump together with healthy proteins and form structures called Rosenthal fibres.These fibres cause damage themselves, but may also cause problems through ‘mopping up’ normal, healthy GFAP or other proteins which are important for the healthy functioning of astrocyte cells.

How is it diagnosed?

If Alexander Disease (AxD) is suspected based on symptoms, patients may have blood tests to rule out other conditions, a magnetic resonance imgaging(MRI) scanto look for the specific pattern of myelin deterioration, and agenetic testto look at the GFAP gene, using a blood or saliva sample. Some (generally older) children have less typical symptoms, which could make diagnosis more difficult. In 5% of people with AxD, no GFAP mutation is found, possibly because it is missed by the test, or because another gene is mutated (changed), with an indirect effect on GFAP function.

How is it treated?

Alexander disease is managed by supporting the patient / family to maximise quality of life. This may include physiotherapy, seizure medication, anti-sickness medications or feeding tubes. Unfortunately, there is currently no treatment available to prevent the disease progressing and most patients will have a severely shortened lifespan, with some children only surviving a few years. The exact life expectancy is dependent on individual circumstances.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Alexander disease is occasionally inherited (less than 0.1 per cent), so affected families may want genetic testing. 

Prenatal diagnosis
If there is a risk of future children being affected, antenatal genetic testing may be possible by chorionic villus sampling or amniocentesis.

Is there support?

Information and support in the UK for Alexander disease is provided by Metabolic Support UK (see entry Inherited Metabolic diseases). Support for dementia can be obtained from the Alzheimer’s Society.

Alzheimer’s Society

Helpline: 0300 222 11 22
Email: via website

TThe Society is a Registered Charity in England and Wales No. 296645, established in 1979. It offers information and advice on all forms of dementia and a network of carers groups, carers’ contacts, befriending projects and helpline. It publishes a monthly newsletter and has information available. The Society has over 25,000 members.

Group details last confirmed June 2017.

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