Lack of testing for adrenoleukodystrophy (ALD) in males who have primary adrenal insufficiency due to an unknown cause may lead to a delayed or missing diagnosis of ALD.
That finding was described in the case report “A 29-year-old patient with adrenoleukodystrophy presenting with Addison’s disease” published in the Endocrine Journal.
In people with ALD, the adrenoleukodystrophy protein is not able to perform its function properly, resulting in the accumulation of a type of fat molecule called very-long-chain fatty acids (VLCFA) in different tissues, including the brain, spinal cord, and the outer region of the adrenal glands (small glands located above the kidneys responsible for the production of many important hormones, including the stress hormone cortisol).
The excessive accumulation of VLCFA in the brain and spinal cord destroys myelin, which is the protective sheath around nerve cells. It damages the adrenal glands, causing primary adrenal insufficiency (PAI), also called Addison’s disease.
ALD can be classified into different types depending on the age at disease onset and if there are any neurological complications. Two types of ALD that involve neurologic dysfunction as an initial symptom include childhood cerebral ALD and adrenomyeloneuropathy.
However, people whose initial symptoms involve PAI are considered to have the Addison’s disease form of ALD. Patients with the Addison’s disease type of ALD also may develop neurological complications as the condition progresses.
In Japan, one in 30,000 to 50,000 boys are diagnosed with ALD, and most ALD cases of Addison’s disease develop during childhood. Notably, only one case of an adult with an Addison’s disease form of ALD has ever been reported in the country.
Now, researchers in Japan discovered another man with Addison’s disease.
The 29-year-old’s symptoms started at age 18 with morning nausea, anorexia, and progressive pigmentation of the skin and tongue. He weighed 45 kilograms (about 100 pounds), which was a 12 kg decrease from when he weighed 57 kg at age 15.
Initial investigations showed his blood levels of cortisol to be low, while the levels of adrenocorticotropic hormone — produced by the brain to stimulate cortisol release — were high. However, in a CT scan his adrenal glands were normal.
Given these symptoms, the patient was diagnosed initially with PAI and prescribed glucocorticoid replacement therapy with a type of cortisol called hydrocortisone.
After further investigation of the underlying causes for his PAI, researchers found that the patient’s levels of VLCFA were high suggesting ALD.
Genetic testing showed he carried a mutation of the ABCD1 gene (the gene defective in ALD), identified as p.Gly116Arg and that already had been associated with ALD in two cases outside Japan.
An MRI showed that at the time the patient did not have any obvious neurologic dysfunction or damage to the brain.
The combination of these findings led to an official diagnosis of Addison’s disease form of ALD.
The patient continued on glucocorticoid replacement therapy and four years after the diagnosis, at age 33, his pigmentation disappeared, and his weight increased to 62 kg (136 pounds). He remained free of any neurological abnormalities or brain damage.
However, different factors contribute to the development of neurological problems in ALD and “predicting his final phenotype [physical manifestation of the condition] is difficult, and close monitoring of neurological complication would be required,” the researchers wrote.
Overall, according to the team, this case report demonstrated that one “should evaluate VLCFA levels in young adult males with idiopathic [of unknown cause] PAI as well as in children for the diagnosis of ALD,” they wrote.
“Early diagnosis enables more rational approaches including the early detection of neurological complications and might improve the prognosis of patients,” the research team added.
