The genetic pathology that attacks the nervous system
Insights on adrenoleukodystrophy
Adrenoleukodystrophy (ALD) is a rare metabolic disease that leads to the progressive loss of the main cognitive, visual and motor functions, leading the subject to a vegetative state. Individuals with ALD (genetic disease) present mutations in the gene that produces ADLP, the protein that helps the body break down long chains of fatty acids: consequently it has an accumulation in the tissues and a consequent damage of the central nervous system cells and adrenal glands.
ALD is a genetic disease that affects the nervous system and exists in different forms. The most widespread is X-linked adrenoleukodystrophy, linked to the mutated X chromosome, inherited only from the mother by the male children. There are, however, some more rare autosomal forms that can affect everyone regardless of gender. Adrenoleukodystrophy in children occurs between the ages of four and eight, with progressive symptoms that vary from subject to subject, leading to a vegetative state around 10-12 years leading to death. The main symptoms are an initial cognitive impairment, vision and hearing problems, hearing and motor function loss. Adrenoleukodystrophy in adults affects subjects over twenty years of age and shows symptoms such as loss of reflexes, disorders of the adrenal glands, neuronal disorders, with a progression rather slow compared to the infantile form.
What are the causes of ALD transmission? X-linked adrenoleukodystrophy, or linked to a gene located on the X chromosome (one of the sex chromosomes) is transmitted to the male children by the mother. In males, endowed with a single X chromosome, the alteration of the gene in each cell is sufficient to cause the disease, since the product of this gene (in this case the ADLP protein) is totally absent. The transmission from affected father takes place on the daughters, but not on the males, to which the father can transmit only the Y chromosome. The females can be carriers because they have two X chromosomes: consequently the ALDP protein will be reduced but not quite absent. A female carrier has the 50% chance to transmit the mutated gene to the sons and the status of carrier to the daughters.
It is not always easy to make a diagnosis of adrenoleukodystrophy. If there are cases in your family history it is good to carry out investigations. One of these is certainly the measurement of the concentration of long chains of fatty acids (VLCFA) in plasma or fibroblasts. The prenatal diagnosis, through the determination of VLCFA in amniotic fluid or chorionic villi allows, starting from the tenth to twelfth week of pregnancy, to detect whether the fetus is affected or not, allowing a timely therapy from birth and slowing down the course of the pathology. Pharmaelle is active in the area of drug research for adrenoleukodystrophy.
For the pathology of ALD and its multiple disorders does not exist still a real therapy. In the case of adrenal insufficiency, adrenal steroids are administered. To reduce the levels of VLCFA, in addition to reducing or eliminating from the diet foods containing long chains of fatty acids, a mixture of fats (oleic acid and erucic acid) has been introduced that produces, to date, an arrest in neurological deterioration in the two thirds of children cared for under six years of age. The current research is mainly focused on the potential of bone marrow transplantation which, if carried out promptly, is able to stabilize and minimize the neurological damage of the disease. In groups of young patients suffering from a clinical trial, bone marrow transplantation gave remarkable results after one year. For more information on specific findings, see the Pharmaelle section of adrenoleukodystrophy products.
- 22 March 2022