Adrenoleukodystrophy (ALD) is a rare metabolic disorder that gradually leads to the loss of the main cognitive, visual and motor skill functions, and thus brings the patient to vegetative state. ALD affected individuals present mutations in the gene which produces the ADLP, the protein that helps the body in breaking down the very-long-chains fatty acids: as a result, these accumulate in the tissues and damage both the central nervous system cells and the adrenal glands.
X-linked Adrenoleukodystrophy: the most common form, linked to the X chromosome
ALD is a genetic disorder that affects the nervous system and exists in various forms. The most common is the X-linked Adrenoleukodystrophy, linked to the mutated X chromosome, inherited from the mother only by male children. There are nonetheless more rare autosomal forms that can affect everyone regardless of sex. In children, Adrenoleukodystrophy manifests between the ages of four and eight; and although its symptoms vary from subject to subject, they gradually worsen leading to a vegetative state around the age of 10-12 that leads to demise. The main symptoms include initial cognitive impairment, visual and hearing problems, loss of hearing and of motor functions. Adult Adrenoleukodystrophy affects individuals over twenty years of age and presents symptoms such as loss of reflexes, adrenal glands disorders, neurological disorders, whose progression is rather slow compared to the childhood form..
Adrenoleukodystrophy: who can pass it along? Parent to child transmission variables
What are the causes of the ALD transmission? The X-linked Adrenoleukodystrophy, or rather the form linked to a gene placed on the X chromosome (one of the sex chromosomes) is transmitted to male children by the mother. In males, whom nature has endowed with a single X chromosome, the alteration of the gene in each cell is enough to cause the disorder, since the action of such a gene (in this case the ADLP protein) is completely absent. Transmission by an affected father occurs on female children, but not on the males, to whom the father can only transmit the Y chromosome. Females can be carrier because they have two X chromosomes: as a result, the ALDP protein is reduced but not completely absent. A female carrier has a 50% chance of transmitting the mutated gene to her sons and the carrier status to her daughters.
Adrenoleukodystrophy diagnosis: how does it happen?
Adrenoleukodystrophy is not always easy to be diagnosed. Investigation is advised in cases where there is a family history of it. One such investigation certainly is measuring the concentration of very-long-chains fatty acids (VLCFA) in plasma or in fibroblasts. Prenatal diagnosis, through the VLCFA dosage in amniotic fluid or in chorionic villi, allows to detect as early as the 10th-12th week of pregnancy whether or not the fetus is affected, by allowing a timely therapy from birth and thus slowing the process down. Pharmaelle is actively taking part in the pharmaceutical drug research for Adrenoleukodystrophy.
Is there a cure for Adrenoleukodystrophy? From diet to bone marrow transplant
To date no real therapy exists for ALD and its multiple disorders. Adrenal steroids are administered in cases involving adrenal insufficiency. To reduce the VLCFA levels, foods containing long-chains fatty acids have been reduced or eliminated from the diet. In addition to this, a fat mixture (oleic acid and erucic acid) has been introduced which, to date, halts the neurological deterioration in two-thirds of the up-to-six-year-old treated. Current research is mainly focused on the potential of bone marrow transplantation which, if performed in a timely manner, can stabilize and minimize the neurological damages. In a clinical trial involving groups of affected young patients, bone marrow transplantation has yielded remarkable results a year later. For further information on specific findings, please visit the Pharmaelle section on Adrenoleukodystrophy products.