New Gene Mutation For Adrenoleukodystrophy Found: A Case Study

When this 20-year-old male patient was serving in the military, he came down with two severe medical issues: pneumonia and adrenal crisis, categorized by an issue with an adrenal hormone called cortisol. Later, says Adrenoleukodystrophy News, the patient was diagnosed with Addison’s disease. But what was causing it? Genetic testing showed that the cause was a novel gene mutation. Read the researchers’ full findings in Endocrinology and Metabolism.


Adrenoleukodystrophy (ALD) is a rare genetic disorder that impacts myelin sheaths, or the protective layer around neuronal nerve cells. People with adrenoleukodystrophy cannot brain down very long chain fatty acids (VLCFA). As a result, VLCFA accumulates in the adrenal gland and nervous system. Adrenoleukodystrophy is caused by inherited mutations in the ABCD1 gene and usually occurs on the X chromosome. Because females have two X chromosomes, they are more likely to be protected from developing ALD symptoms than males.

Types of Adrenoleukodystrophy

There are multiple types of adrenoleukodystrophy. These include:

  • Female ALD: this is the least common form of adrenoleukodystrophy. Patients with female ALD generally do not experience symptoms until after 35 years of age. Symptoms include numbness, urinary problems, joint pain, and progressive lower leg weakness. Patients with female ALD do not have Addison’s disease.
  • Childhood cerebral demyelinating ALD: in contrast, this is the most common form of ALD. Symptoms first occur between the ages of 4 and 10. These include vision and hearing loss, epilepsy, ADD, progressive intellectual and mental decline, increased aggression, muscle spasms, loss of muscle control, and Addison’s disease. This condition is generally fatal within 5 years of diagnosis.
  • Adrenomyeloneuropathy (AMN): This subset of ALD experiences symptom onset between ages 21-35. Symptoms include loss of body movement control, lower limb paralysis, progressive motor weakness, and Addison’s disease. While people with AMN can live five years or longer, the condition is ultimately fatal.

Learn more about adrenoleukodystrophy.

Addison’s disease

Addison’s disease is the 4th form of adrenoleukodystrophy. In 10% of patients with ALD or AMN, the presence of Addison’s disease is the only symptom. This disease occurs when the adrenal glands fail to produce enough cortisol and aldosterone. These hormones are very important to bodily function. Aldosterone regulates salt and water levels, impacting blood volume and pressure. On the other hand, cortisol assists with inflammation, helps raise blood sugar, and controls nutrient flow and water levels.

Addison’s disease develops following damage to the adrenal glands. Additionally, AIDS, surgery, fungal infections, cancer, or autoimmune reactions can cause Addison’s disease. Symptoms include irritability and depression, fainting, fatigue, weight loss, craving salt, nausea, darkened skin patches, and low blood pressure. Learn more about Addison’s disease.

Case Study

After the patient was referred to an endocrinologist, he participated in various diagnostic testing to better understand his condition. Researchers discovered high levels of VLCFAs, which suggest adrenoleukodystrophy. Next, researchers sequenced the patient’s DNA.

The sequencing revealed genetic mutation c.1991G>A, which contributed to protein mutation p.Trp664*. (p.Trp664*, c.1991G>A) is considered a nonsense mutation. According to the National Human Genome Research Institute, a nonsense mutation:

is the substitution of a single base pair that leads to the appearance of a stop codon where previously there was a codon specifying an amino acid. The presence of this premature stop codon results in the production of a shortened, and likely nonfunctional, protein.

The “stop” halts the gene in the middle of translation. Uniquely, this genetic mutation is novel. Basically, this gene never before appeared in patients with adrenoleukodystrophies. However, because testing showed VLCFA buildup, it suggests that the mutation caused the patient’s adrenoleukodystrophy.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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