Adrenoleukodystrophy (ALD)
X-Linked Adrenoleukodystrophy, cerebral ALD See also: Adrenomyeloneuropathy
Inheritance:
X-linked Inheritance
Age range at onset:
Any
(most common onset between ages of 4-10)
Specialists you may see:
Symptoms
Males with ALD have the potential to develop one or more of the three conditions that are related to the gene. Females do not develop the most severe forms of ALD (cerebral ALD or adrenal insufficiency). It’s not possible to tell in advance how any individual person will be affected.
In cerebral Adrenoleukodystrophy (ALD), nerves in the brain no longer work properly, and the person’s physical and mental abilities begin to deteriorate. Functions such as reasoning, speech and mobility are lost. Eventually, they become completely dependent. Medical guidelines say that boys with cerebral ALD will live for another 2 to 4 years. But many boys have gone on to live for longer periods. There are boys with the condition who are living into their teens and early 20s with quality of life. Sadly, there is currently no treatment for cerebral ALD once it has begun causing symptoms. Doctors have not yet found a way to stop the deterioration once it takes hold. However, if the disorder is detected in the very early stages, when few if any symptoms are visible, it is usually possible to stop it progressing. Those with ALD in its early stages (Asymptomatic) should have regular MRI scans so that early signs of cerebral ALD can be picked up quickly and treatment can be given.
In most males with ALD the adrenal glands are also affected. The adrenal glands make steroid hormones. Poor functioning of these glands is known as adrenal insufficiency, or Addison’s Disease.
Cause
ALD is caused by a genetic fault that means those affected are unable to process Very Long Chain Fatty Acids (VLCFAs). It is thought that these VLCFAs accumulate and destroy the myelin sheath that covers the nerves in the body and brain. The myelin (white matter) acts like the coating around an electric cable, and allows messages to be transmitted along nerve cells.
The gene at fault in ALD is called ABCD1. The faulty gene can cause several related but different conditions, such as Asymptomatic ALD (for males affected by the gene who do not yet have symptoms). In cerebral ALD, the damage to the myelin happens in the brain. The other condition caused by the faulty ABCD1 gene is called Adrenomyeloneuropathy (AMN), which affects nerves in the spinal cord and body.
News, research and treatment
Bone Marrow Transplants (BMT) (or stem cell transplants) are the most common tried and tested treatment for boys with early stage ALD, usually before any physical symptoms have appeared. The success rate is increasing all the time, at 90-95% in 2016. Gene Therapy is also in development; initial results have been promising. Transplants in adults who are showing signs of cerebral ALD are not common, but practices are changing. It is recommended that all cerebrally asymptomatic adults access yearly MRI scans if they want them.
Research journal article: Long-term outcomes of allogeneic haematopoietic stem cell transplantation for adult cerebral X-linked adrenoleukodystrophy
New Born Screening for ALD would allow more boys with ALD to receive treatment before the condition progresses. This has been introduced in parts of the USA, and Alex TLC are actively involved in efforts to introduce it in the UK
Link between Addison’s Disease and Adrenoleukodystrophy