Adrenoleukodystrophy (ALD)

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Adrenoleukodystrophy (ALD) is a genetic disease that is linked to the X chromosomes and because of this, it is also X-linked Adrenoleukodystrophy or X-linked ALD. ALD affects the adrenal glands and the nervous system. The condition is a rare one that occurs in 1 person in about 20,000 to 50,000 people and this occurs mainly […] Read More

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Adrenoleukodystrophy (ALD)

Adrenoleukodystrophy (ALD) is a genetic disease that is linked to the X chromosomes and because of this, it is also X-linked Adrenoleukodystrophy or X-linked ALD. ALD affects the adrenal glands and the nervous system. The condition is a rare one that occurs in 1 person in about 20,000 to 50,000 people and this occurs mainly in males. If a female has the ALD gene, there will be no symptoms, or the symptoms will be very few and mild.  What is Adrenoleukodystrophy? ALD disease is a rare hereditary condition that makes the body unable to break down very-long-chain fatty acids (VLCFAs). Due to the inability to be broken down, the VLCFAs piles up in the brain, adrenal glands, and nervous system.  The accumulation of VLCFA causes damage to the myelin sheath (the membrane that protects nerve cells in the brain from getting harmed). The nerve cells are the nerves responsible for brain function and when the myelin sheath is destroyed, they can no longer pass information to and from the brain. This can result in several brain dysfunctions. There are different types of X-linked ALD. The common types include:
  • Cerebral ALD (CALD)
There are different names for this disorder; “cerebral demyelinating ALD”, “childhood cerebral ALD”, “childhood on-set ALD”. It is referred to as “childhood” because it happens to children between the ages of 3 to 10. The condition damages the white area of the brain, progressing rapidly and causing severe and irreversible brain disability. It can lead to a permanent disability and death if not diagnosed and taken care of on time.
  • Adrenomyeloneuropathy (AMN)
This disorder occurs in adults and is milder than cerebral ALD. A person with this gene does not have an occurrence of symptoms until they are in their 20’s to 30’s. The damages in this condition progress slowly and are less severe but can lead to a loss of brain function. But due to the slow progression, the damages can be notably controlled if symptoms are discovered early.
  • Addison’s Disease
This disorder is also known as “adrenal insufficiency” because it happens when there is low production of hormones by the adrenal glands. This can weaken the patient in general and cause severe damage to the brain.
  • Female ALD
It is a fact that ALD rarely affects females. However, the genes can be found in females, but symptoms hardly manifest because they have more than one X chromosome. If the symptoms do manifest, they are very mild and may lead to no brain damage. Often, these symptoms occur after they are 35 years. Diagnosis Your doctor will go through your medical and family history incognito with your symptoms. However, ALD has symptoms that can be related to other mental and behavioral problems. So, further tests will have to be performed to confirm the disorder. They include:
  1. Blood Test; to check your adrenal glands and how well they are functioning, find the mutated genes and check for the presence of a very high level of VLCFAs.
  2. Magnetic Resonance Imagery (MRI); to examine the abnormalities and damage in the brain that can be an innovation of ALD.
  3. Biopsy; to examine a small sample of skin for the high level of VLCFAs
  4. Fibroblast Cell Culture (FCC); checks a patch of skin cell for accumulated levels of VLCFAs.
Treatment ALD can not be cured, but the symptoms can be controlled and its progression can be slowed down. The control treatments depend on the type of ALD you are diagnosed with. Treatments include:
  • Bone Marrow (Stem cell) Transplant
This is mostly done to slow the progress of symptoms of cerebral ALD. However, it is helpful for children who have early signs of this disorder. The healthy blood cells in the transplanted stem cells can prevent nerve damage of the brain and make them live near-normal lives.
  • Gene Therapy
This is a newly developed treatment, still on a clinical trial for cerebral ALD treatments. This therapy removes the diseased stem cells, repairs the mutated gene, and puts the repaired gene back. The results from the clinical trials have been encouraging and a record of 88% of boys who undertook the therapy had the progression of the condition controlled. The risk is also fewer than that of stem cell transplants. More research is being conducted to make the treatment method safe and long-lasting, so if you are considering this treatment, your consent along with a family member and a legal backing.
  • Steroids
Corticosteroid replacement pills or injections can be used to treat adrenal insufficiency (Addison’s disease).  
  • Medications
Drugs to relieve the symptoms of ALD such as seizures, headaches, stiffs, cramps, etc, can be prescribed by your doctor.
  • Physical Therapy
A physiotherapist can provide you with an exercise routine that can strengthen your muscles, reduce the rigidity of the muscles, and ease the cramps.
  • Diet
Being on a diet that has a low level of VLCFAs can help control the build-up of the acids in the blood.


Symptoms of ALD

The symptoms of adrenoleukodystrophy depend on the type that affects you. They include the following:

Cerebral ALD:

  • Attention deficit disorder (ADD); poor memory and short attention span.
  • Literacy problems such as difficulty in reading and writing.
  • Poor language and speech comprehension.
  • Problems with movement and metabolism.
  • Impaired hearing and vision.
  • Hyperactivity
  • Rapid behavioral changes; aggression or withdrawal.
  • Pale skin
  • Weakness and clumsiness
  • Low blood sugar
  • Crossed eyes and eye pains
  • Swallowing difficulty
  • Muscular cramps and spasms
  • Infections occur often.
  • Migraine

If the situation worsens and there are no treatments, there may be cases of:

  • Speaking inability
  • Seizures
  • Paralysis
  • Coma
  • Death.

Adrenomyeloneuropathy (AMN): 

  • Problems in remembering and thinking.
  • Muscular weakness; arms and legs.
  • Inability to maintain balance.
  • Unstable gait/movement.
  • Tingly sensations and numbness in legs.
  • Poor erectile function.
  • Inability to control urination and stopping.

Addison’s Disease: 

  • General body weakness
  • Weakened muscles
  • Low appetite 
  • Nausea and vomiting
  • Loss of weight
  • Darkened patches of skin
  • Low blood pressure
  • Abdominal cramps and pains

Female ALD: 

  • Fatigue
  • Muscular numbness
  • Pains in the joint
  • Urinary problems.


Causes of ALD

Adrenoleukodystrophy is caused by the mutation of the ABCD1 gene in the X chromosome. The ABCD1 gene makes the adrenoleukodystrophy protein (ALDP), which is responsible for breaking down and transporting very-long-chain fatty acids (VLCFAs) into the peroxisomes for processing and around the body.

When the genes are mutated, they become distorted and can no longer produce enough ALDP to break down and transport VLCFAs, therefore, leading to their accumulation of the fatty acids in the body. In their unprocessed state, they begin to destroy the nerve cells connected from your brain to the adrenal glands, spinal cord, etc, blocking out nerve signals, and causing the brain to begin losing its function.

ALD is mainly common in males than females because males have just one X chromosome, so they get to inherit the defective chromosome from a parent and it begins to affect them and is very severe. Meanwhile, females have two X chromosomes and get to only one copy of the defective gene, hence symptoms may not be present or may be mild because the healthy ABCD1 gene in the X chromosome makes enough ALDP keep the VLCFAs broke down and well transported.


How common is ALD?

ALD is a very rare disorder that is said to happen in about 1 in 20,000 to 50,000 people worldwide.

Can ALD appear without a known family history?

Only in very few cases–about 5 to 7%–, can a person develop ALD which a genetic transfer. In this rare case, the ABCD1 gene mutates randomly and on its own without a genetic trigger. This is called the “de novo mutation”.

What is CALD?

CALD is cerebral adrenoleukodystrophy, a type of ALD that happens to male children of 3 to 10 years. It is a very chronic ALD disorder that progresses rapidly and can lead to a vegetative state and then death if not treated early enough.

How long can a child live with childhood cerebral adrenoleukodystrophy?

CALD is a very fat progressive disease and if not detected and treated in the early years of your child can bring irreversible complications. The symptoms begin showing from the age of 3 to 4 and if not tackled, in about 2 years, he can go into a long-term vegetative state (coma) for as long as 10 years before death.

Can you survive ALD?

The prognosis for this disorder is poor, especially for cerebral ALD. Unless treated, a child can survive CALD for only 5 to 10 years, while in Adrenomyeloneuropathy (AMN) and Addison's disease, a survival rate of 10 to 15 years is estimated.