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Adrenoleukodystrophy (ALD)

To explain the desease adrenoleukodystrophy (ALD) you have to start by parsing the name.

  • Adreno means that the adrenal glands (adrenes) are involved.
  • Leuko means white, which refers to the white color of myelin, the protective layer that surrounds nerve tissue in the brain and conducts the stimuli.
  • Dystrophy means poorly fed.

The white matter (myelin) in the brain is not properly built up or is damaged. The adrenal glands are also involved in the disease process.

 

ALD disease was previously known as 'Schilder-Addison's Disease'. The disease is progressive in nature, which means that the symptoms increase and can lead to death. The disease is relatively rare.

Adrenoleukodystrophy (ALD) is also known by the filmed search of Lorenzo Odone's parents for treatment in the film Lorenzo's Oil.

 

Demyelination

Adrenoleukodystrophy is a metabolic disease that affects the myelin in the brain, spinal cord and peripheral nerves (nerves in the extremities of the body) (central and peripheral demyelination).
It decreases the function of the adrenal cortex and the testicles in men. White matter abnormalities can be seen on an MRI scan.

 

Hereditary disorder

The letter X for the name of the disease X-ALD indicates the hereditary origin located on the X chromosome, namely Xq28. The ALD gene was discovered in 1993. Because men have one X chromosome and one Y chromosome and women have two X chromosomes, the complaints in women can be milder because the other X chromosome protects them slightly.

How much chance there is of having a sick child can be read in this image. It was previously believed that women could only be carriers of the disease, but symptoms occur in 4% of women who are carriers.

 

Metabolic disease

X-ALD is a metabolic disease in which substances in the cells in the body are processed less well. It is a so-called peroxisomal metabolic disease in which the peroxisomes, the parts of a body's cell that break down waste products, do not function properly. This causes damage to the brain tissue and other organs. In the case of X-ALD, certain fatty acids, very long chain fatty acids (ZLKV), accumulate.
It is still being investigated how these very long-chain fatty acids can cause myelin attack and loss. The very long-chain fatty acids are also known as very long-chain fatty acids (VLCFA).

 

Different forms of ALD

The names for the different forms of ALD are related to the age at which the disease manifests itself:

  • Childhood cerebral ALD / childhood-onset ALD (CCALD.

Complaints start between the third and tenth year of life.

  • Extensive white matter abnormalities can be seen on an MRI scan
  • Cognitive disorders
  • Behavioral disorders
  • Tractus corticospinalis disorder

 

  • Adolescent cerebral ALD (AdolCALD).

Complaints occur between the tenth and twenty-first year of life.

Complaints are similar to those of CCALD.

  • Complaints start stealthily.
  • Complaints often start with:
    • Behavioral disorders
    • Cognitive impairment, decreased school performance
    • Vision problems
    • Poor hearing / deafness
    • Epilepsy
    • Weakening of all four limbs (tetraparesis)
    • Spasticity
    • Rare: polyneuropathy. Polyneuropathy is a condition in which nerves are affected in several places in the body with pain, numbness, tingling or tingling.
    • Extensive white matter abnormalities can be seen on an MRI scan.
    • Tractus corticospinalis disorder
    • Usually, the adolescent form is associated with Addison's disease. In addition, the adrenal cortex does not produce enough hormones with significant consequences.

 

  • Adult cerebral ALD (ACALD).

Complaints occur after the twenty-first year of life.

Complaints are similar to those of AdolCALD.

  • The following complaints also arise:
    • Can be accompanied by dementia
    • Can be accompanied by psychiatric syndromes

 

Non cerebral ALD forms

  • Adrenomyeloneuropathy (AMN) in which the brain is not affected. AMN is often accompanied with Addison's disease, and impaired function of the gonads (gonadal dysfunction). Wallerian degeneration of the tractus corticospinalis occurs. Slow progression. Absence of behavioral changes and cognitive impairment. Tractus corticospinalis disorder.
  • Addison-only where the brain is not affected. The frequency that this disease occurs decreases with age. It occurs from the second year of life. No tractus corticospinalis disorder. Addison's disease always occurs with this form.
  • Asymptomatic or pre-symptomatic X-ALD. The disease has been detected in the hereditary material, blood or cultured skin cells, but no symptoms occur. There is a chance that symptoms will develop.

 

Possible complaints

The complaints are very diverse, even within families with this condition. A combination of all characteristics occurs in 30% to 50% of the boys.

  • Deterioration of neurological functions,
  • Convulsions,
  • Disturbed balance,
  • Uncoordinated movements of limbs and trunk (ataxia),
  • Deterioration of hearing and vision,
  • Concentration disorders,
  • Changed, disturbed behavior,
  • Epilepsy is sometimes the first symptom,
  • Tractus corticospinalis disorder
  • Addison's disease (in 75% of those affected) in which the adrenal cortex does not produce enough hormones causing:
    • a shortage of cortisol, a stress hormone that plays a role in physical and mental exertion, normal bone production and bone breakdown processes (bone metabolism), regulates day and night rhythm, inhibits inflammation, increases blood sugar and blood pressure in stressful situations. A lack of cortisol can be life-threatening and is called an Addisonian crisis,
    • a deficiency of aldosterone that plays a role in the fluid balance by maintaining water, sodium and potassium balance and in maintaining blood pressure,
  • Unresponsive wake syndrome / vegetative state

This table (in Dutch) lists the complaints per ALD form.

 

More information

The website for rare diseases Orphanet pays attention to ALD.

Information on Peroxisome biogenesis disorders can be found on this website.

An information platform on ALD on this website.