Adrenoleukodystrophy/Adrenomyeloneuropathy

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Rare types of adrenal insufficiency: ALD

What is Adrenoleukodystrophy/Adrenomyeloneuropathy

X-linked adrenoleukodystrophy (ALD) is a rare inherited male-limited disorder that can affect the nervous system and the adrenal glands. Its prevalence is estimated at about 1 in 50,000 individuals. There are three types of X-linked adrenoleukodystrophy: a childhood form with cerebral neurologic problems, adrenomyeloneuropathy (AMN) with combined adrenal insufficiency and neurologic problems, and form with adrenal insufficiency or Addison disease only.

ALD is in the class of peroxisomal storage diseases, and is caused by the inability to break down very long chain fatty acids (VLCFA). When these fatty acids accumulate, they interfere with the transmission of nerve signals. Neurologic dysfunction may coexist with adrenocortical insufficiency due to parallel toxic effects of VLCFA on adrenal steroid hormone production.

Children with the cerebral form of X-linked adrenoleukodystrophy begin to show signs of learning and behavioral problems between the ages of 4 and 10. The symptoms eventually worsen, and may lead to severe physical and mental disabilities by young adulthood. Adrenal insufficiency is variably present. Careful endocrinologic testing must be done to diagnose this problem, as it is often subtle at first.

The age of onset for adrenomyeloneuropathy is typically in early adulthood, but can be later. Symptoms include leg stiffness and weakness, genito-urinary tract disorders, and behavior changes. Addison disease is common in AMN.

The Addison disease only form presents anytime from early childhood through adult life with non-specific symptoms and signs of weakness, weight loss and failure to thrive, skin darkening, vomiting, and shock. Lifelong replacement hormones (usually oral glucocorticoids and mineralocorticoids) are required in such cases, and will usually prevent episodes of acute adrenal insufficiency. Patients should wear and/or carry a medical identification tag specifying adrenal insufficiency.

Life expectancy depends on the severity of the signs and symptoms, timing of the diagnosis and treatment for adrenal insufficiency. Female carriers of the ALD trait may show mild symptoms.

ALD is caused by mutations in the ABCD1 gene that codes for a protein known as ALD protein (ALDP). A deficiency of ALDP prevents breakdown of VLCFAs that trigger an inflammatory reaction and consequent destructive changes in the adrenal cortex and brain myelin. Genetic testing and counseling should be offered to families of ALD patients. Any male with adrenal insufficiency should be tested for ALD.

There is no cure at present for ALD, however, research is underway directed at ameliorating disease progression. Children who have no neurologic abnormalities may benefit from Lorenzo’s Oil that appears to prevent VLCFA accumulation. Some trials will attempt to demonstrate whether stem cell transplants are therapeutic. For details concerning current research and compassionate use trials, see: https://clinicaltrials.gov/ct2/results?term=adrenoleukodystrophy&Search=Search

Additional resource: ALDconnect.org

ALD Connect is an organization dedicated to improving the health outcomes for patients with adrenoleukodystrophy (ALD). They offer ways for patients and health providers to better connect, and offer tools to help educate and raise awareness. ALD Connect is working to develop a strong social network for patients and advocates for support and to promote guidance in research and advocacy for ALD. Their website offers tools to help find research trials for various related illnesses.