Adrenomyeloneuropathy

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

Adrenomyeloneuropathy or AMN for short, is one form of X-ALD (also known as X-linked adrenoleukodystrophy or simply adrenoleukodystrophy). Adrenomyeloneuropathy is a rare genetic disorder in which affected individuals typically do not show symptoms until they are in their late 20's.

Contents

Definition & Facts

Adrenomyeloneuropathy is a type of demyelinating disease in which the myelin which is a fatty covering over the nerves of the spinal cord and brain becomes destroyed (demyelination). Other demyelinating diseases include multiple sclerosis, optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, neuromyelitis optica, central pontine myelinolysis, extrapontine myelinolysis, acute haemorrhagic leucoencephalitis, and progressive multifocal leucoencephalopathy.

Adrenomyeloneuropathy causes severe neurological symptoms and primarily affects men more than women because the genetic mutations associated with the disease are inherited via the X chromosome, of which women have two thus reducing their risk. Adrenomyeloneuropathy is an inherited condition that presents equally across diverse ethnic populations. The genetic mutation that causes adrenoleukodystrophy (which includes adrenomyeloneuropathy) was discovered in 1993.

Adrenoleukodystrophy received much media attention through the film, Lorenzo's Oil which came out in 1993. A therapy of that same name – Lorenzo's oil which consists out of oleic and erucic oil – has been studied for its efficacy in treating adrenoleukodystrophy and in preventing certain types of adrenoleukodystrophy from worsening.

There are two major types of adrenomyeloneuropathy as follows:

  • Adrenomyeloneuropathy (without cerebral involvement). Considered a less serious form of adrenomyeloneuropathy, individuals diagnosed with this form will have symptoms that relate to spinal function only. 
  • Adrenomyeloneuropathy (with cerebral involvement). Considered a more severe form of AMN, individuals will experience mild impairment with brain development and cognitive impairment over time, while some may experience severe and progressive brain impairment that leads to a persistent vegetative state or death.

In general, women who have adrenomyeloneuropathy often have only mild symptoms or are totally asymptomatic, and they are just carriers of the genetic mutation that causes AMN. To date, the majority of symptoms and the most severe cases have appeared in males.

Symptoms & Complaints

Common symptoms of adrenomyeloneuropathy include the following:

Causes

Adrenoleukodystrophy arises when the ABCD1 gene mutates. The mutation leads to deficiencies in a certain essential protein called adrenoleukodystrophy protein (ALDP). ALDP is responsible for keeping levels of very long chain fatty acids (VLCFAs) in check. It helps the body transport and break down these substances.

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 as well as causes damage to the adrenal glands. 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 adrenomyeloneuropathy is typically done by testing the blood for the presence of very long chain fatty acids (VLCFAs). If elevated levels are found in the blood, this is considered indicative of adrenomyeloneuropathy. For further confirmation, a blood test that looks for insufficiency of common adrenal gland hormones can also be done.

Once blood tests indicate that adrenomyeloneuropathy is a likely diagnosis, the physician will often order a magnetic resonance imaging (MRI) test to look for impairment in cerebral structure or function. Neurological examinations will also be performed to assess the presence and severity of symptoms.

Treatment & Therapy

At this time, treatment for adrenomyeloneuropathy focuses on symptom reduction and management. Because there are so many different possible symptoms depending on the type and severity of each case of adrenomyeloneuropathy, the treatment will always be tailored to each individual patient's symptoms and needs. Common treatments prescribed for adrenomyeloneuropathy include the following:

  • Attempting to remedy insufficient adrenal hormone levels with drugs that contain cortisol and other hormones so the body can regulate blood pressure among other processes and functions
  • Dietary changes with Lorenzo's oil supplementation – Lorenzo's oil is a combination of two oils- oleic oil and erucic oil. While the efficacy of this is still inconclusive and being studied in clinical trials, taking Lorenzo's oil while eating a diet that is low in VLCFAs may keep the overall level of VLCFAs in the body lower and perhaps halt impairment of brain function. Initial studies indicate that Lorenzo's oil is most efficacious in those diagnosed with adrenoleukodystrophy prior to the presentation of symptoms and for those with childhood cerebral adrenoleukodystrophy, a different and more severe type of adrenoleukodystrophy than adrenomyeloneuropathy.
  • Anti-seizure medications. These medications can reduce the risk of AMN seizures.
  • Physical therapy. Movement therapy can help ease muscle spasms and stiffness associated with AMN. 

Adrenomyeloneuropathy is a chronic, degenerative disease, but its prognosis is still better than that of childhood cerebral adrenoleukodystrophy. In milder cases of adrenomyeloneuropathy, and especially those where symptoms do not appear until much later in life, progression of the disease can be much slower, which can delay the need for treatment.

Prevention & Prophylaxis

There is currently no known cure for adrenomyeloneuropathy. There is no way to prevent transmission of the gene mutation responsible for adrenomyeloneuropathy, unless couples choose to undergo genetic counseling during family planning

For individuals who have cases of adrenomyeloneuropathy in their family, genetic testing is typically recommended. If this is the case and a pregnancy is already underway, prenatal diagnosis via amniocentesis or chorionic villus sampling can discover if the fetus has the gene mutation.