Adrenomyelopathy: Risk Factors, Etiology, Genetics, Symptoms, Diagnosis, Treatment and Prevention

It is a category and adult form of the disease known as adrenoleukodystrophy.

It is a rare metabolic disease transmitted through genes, so the unborn suffer from it during the gestation process but suffers it after adolescence, with an estimated age of 20 years.

Adrenomyelopathy is linked to the X chromosome and associated with an accumulation of saturated fatty acids in both tissues and body fluids.

This condition shows signs of adrenal insufficiency before the onset of neurological symptoms.

Risk Factors for Adrenomyelopathy

As this condition or disease occurs in a family history of adrenoleukodystrophy, heredity is almost inescapable, so a couple of future parents must undergo various medical and genetic studies to confirm or diagnose the condition in time in the unborn.

Etiology and genetics of Adrenomyelopathy

This condition affects or interrupts the regular activity of the adrenal gland and testes due to the accumulation of long-chain fatty acids in the nervous system.

It is transmitted by genes from parents to children through the X chromosome. However, its appearance appears in most cases in males in an age range of 20 years or later.


Women can have the disease in milder form and are often the carriers.

Approximately 1 in 20,000 people of all races and geographic areas are affected by adrenoleukodystrophy, including two other major categories of the disease.

The infantile brain form is characterized by a more severe onset of neurological symptoms between 5-12 years of age. The other type of disease in the category affects the function of the adrenal gland by altering it. It is also known as Addison’s disease.

This condition usually affects the adrenal gland because it does not produce enough steroid hormones.

Genetically speaking, the ALD gene is located in the Xq28 region of the X chromosome and contains ten exons, and encompasses 20 kb of genomic DNA. These genetic codes for the ALD protein have been localized to the peroxisomal membrane.

The gene is subject to X chromosome inactivation placing implications for female members (XX) of a family with an inherited X-linked disorder.

In this inactivation process, one of the two chromosomes becomes condensed, inactive, and permanently random, occurring in the embryonic stage.

If the defective allele is on the chromosome inactivated, there will be no phenotypic manifestation of the disease. However, if the defective allele is on the active X chromosome and the other inactive, there will be a clinical expression of the disorder.

A scientific study analyzing the ALD gene mutation in 35 individuals with this unrelated condition revealed that all had ALD X-q28 gene mutations within this group.

Resulting in that six percent had large deletions, and 17% had an AG deletion in axon 5.

The remainder had “private” mutations specific to each kindred, of which 55% had mutations, and 30% had frame-shift mutations; nonsense mutations occurred in 8% and splice defects in 4%.

There is no correlation between the nature of the mutation and the phenotype that has been detected.

Symptoms of Adrenomyelopathy

Symptoms of this condition include:

  • Adrenal dysfunction.
  • Muscle weakness or stiffness in the legs can get worse over time.
  • Difficulty with visual memory and quick thinking.
  • Problems controlling urination.

Detection and diagnosis of Adrenomyelopathy

Laboratory investigation of blood samples may show very long and high chain levels of fatty acids. Peripheral nerve biopsy has revealed characteristic inclusion bodies in Schwann cells.

Chromosome studies can help demonstrate the specific gene for mutation. The MRI will reveal images of the damaged white matter in the brain.

Treatment and therapy

Specific treatment for X-linked adrenomyelopathy is not available, but steroids such as cortisol often treat the dysfunction.

Ingested oils called Lorenzo’s oil are being tested as a treatment to lower the levels of very-long-chain fatty acids in the blood.

Bone marrow transplantation is also being considered as a potential treatment.

Prevention and results

A genetic study is recommended for prospective parents who have a family history of adrenoleukodystrophy. Because it is a sensitive test that denotes very-long-chain fatty acids and a DNA probe study performed by specialized laboratories can diagnose the carrier status in 85% of female cases.

Through amniocentesis, the disease can be diagnosed prenatally.

The results of adrenomyelopathy are milder than the infantile form of adrenoleukodystrophy which is described as progressive and leads to a long-term coma within approximately two years after the development of neurological symptoms.