Adrenoleukodystrophy

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at September 1, 2016
StartDiseasesAdrenoleukodystrophy

Adrenoleukodystrophy (ALD) is a group of medical conditions that involve the central nervous system and the adrenal glands. There are three types of adrenoleukodystrophy: childhood cerebral ALD, adrenomyeloneuropathy, and Addison disease only. It is a type of demyelinating disease. Another name for this condition is X-linked adrenoleukodystrophy.

Contents

Definition & Facts

Adrenoleukodystrophy is a rare genetic disorder that affects about 1 in 20,000 to 50,000 people. It mainly affects males. Females who have the genetic defect that is responsible for the illness usually don't have symptoms or have mild symptoms. 

There are three forms of the illness:

  • Childhood cerebral ALD - This form of the condition affects children who are three to ten years of age. It develops quickly and results in severe disability or death.
  • Adrenomyeloneuropathy (also called AMN) - This form mainly affects adult males. It is a milder form than childhood cerebral ALD. Also, it develops fairly slowly. 
  • Addison-only disease - This form of the illness happens when the adrenal glands don't produce enough hormones such as cortisol (adrenal insufficiency). 

Symptoms & Complaints

The childhood cerebral form of ALD starts between four and eight years of age. Its symptoms include:

Adrenomyeloneuropathy starts in the late twenties, can take decades to progress, and has the following symptoms:

Those with Addison-only version typically experience the same symptoms as those with adrenomyeloneuropathy by the time they reach middle age. In addition, dementia and mental disorders have been features of rare incidences of adrenoleukodystrophy.

Causes

The protein, adrenoleukodystrophy protein (ALDP) helps the body transport and break down very long chain fatty acids (VLCFA's). People with ALD have mutations in the gene, ABCD1 that produces ALDP. This results in less ALDP which then causes the level of fatty acids to rise inside of the body.

The increase of very long chain fatty acids is believed to trigger an inflammatory response which then causes damage to the myelin sheath which covers the nerves in the spinal cord and brain and causes damage to the adrenal glands. The process whereby the myelin is destroyed is called demyelination.

Males are usually affected by the condition at a younger age than females. ALD attacks males more than females because it is linked to the X chromosome

Diagnosis & Tests

Diagnosing the condition can be difficult because the symptoms are similar to other neurological conditions. To diagnose the condition, the doctor will go over the symptoms and the patient's medical history and his or her family history. The doctor will conduct a physical examination and order various tests. 

  • Blood testing- These tests look for high levels of very long chain fatty acids in the blood. This is a main indicator of the illness. The doctor will use blood samples for genetic testing to look for defects or mutations that are responsible for ALD. They also will use blood tests to determine how well the adrenal glands work. 
  • Magnetic resonance imaging (MRI)- Magnets and radio waves produce detailed pictures of the brain. This will allow the doctor to discover abnormalities in the brain. This includes damage to the white matter of the brain. 
  • Eye examinations- The doctor will measure visual responses to detect the progression of the disease. 
  • Biopsy- A small sample of skin will be taken to check for very long chain fatty acids. 

Treatment & Therapy

The use of Lorenzo's oil has been studied in various clinical trials as a treatment and preventative medicine for treating childhood cerebral ALD. Lorenzo's oil is a mixture of oleic acid and erucic acid which may help reduce the levels of very long chain fatty acids which are known to cause ALD. Research has shown that the substance might be good for preventing the onset of symptoms in boys who do not have symptoms yet. Nevertheless, its efficacy is debated and controversial.

Stem cell transplantation may also be an option for some cases of adrenoleukodystrophy. The source of the stem cells is either from an umbilical cord or from bone marrow. The aim is to give the patient healthy stem cells that create a functioning ALD protein.

Treating adults who have adrenomyeloneuropathy is very limited. At present, doctors will not recommend stem cell transplantation on adults. The risks of the treatment outweigh the potential benefits. As the technology improves, transplantation may become useful for adults.

Treatment will also rely on alleviation of symptoms and can take the form of special education, physical therapy, speech therapy, and psychotherapy to cope with the challenges of this degenerative disease.

Prevention & Prophylaxis

The ALD genes can be identified either by testing women before they become pregnant or by performing prenatal testing during pregnancy. The prognosis of people with the illness varies a great deal. It is most severe for people with the childhood, adolescent, or adult cerebral forms.

The progress of the illness is quick and many times leads to a persistent vegetative state within two years of onset. The duration of life depends on the ability to avoid the complications of confinement to bed and the necessity of total support services. The prognosis for patients with adrenomyeloneuropathy is more favorable.