Dr Shoji Tsuji.
Tokyo University Hospital.
The International University of Health and Welfare Genomic Medicine Research Institute.
Aadrenal leukodystrophy originally developed in boys of school age, and is called the white matter Inflammatory demyelination in the area where nerve fibers are gathered and pass) is a disease in which the nervous system covering the nerve fibers is impaired. It has been identified as a disease that progresses throughout life Previously, it was called Schilder’s disease, taking the name of the doctor who originally diagnosed the disease, or Dr. Masahiro Ishige, who went to Albert Einstein University in the United States in 1976,
In the developing brain, they discovered that very long fatty acids with 24, 25, and 26 carbon atoms, known as very long spot defenses, accumulated as specific cholesterol esters. This discovery led to the elucidation of the biochemical abnormalities of the disease, and later made it possible to make a biochemical diagnosis using blood. The disease can be manifested as slowly progressive gait disorders (called adrenal spinal cord neuropathy), not only in school-age boys but also in adult men,
It has been revealed that there are various clinical types of this disease, such as cases in which there are no symptoms but only a decrease in the functions of the adrenal cortex, one of the endocrine organs (similar to Addison’s disease). The disease is caused by a gene called ABCD1, which encodes a protein that resides in the membranes of organelles inside the cell called veloxisomes, which converts very long-chain fatty acids into the cytoplasm. Is thought to play a role in linking to the veroxisome.
Veroxisomes work by partially degrading very long chain fatty acids and then passing them on to the mitochondria for complete degradation. It is thought that abnormal function of the protein produced by ABCD1 causes the accumulation of extremely long fatty acids in the cytoplasm, which is thought to cause this disease, but the detailed mechanism is still unclear. It has not yet been established.
The 10COL gene is located at the end of the long arm of the X chromosome at a location called Xq28. The X and Y chromosomes have one sex chromosome Lin clot. Therefore, the number of female X chromosomes
Niimi also shows progressive obstruction (referred to as adrenal spinal cord neuropathy) or no neurological symptoms, but only a decrease in intercortical function, which is one of the internal organs (Showing symptoms similar to a disease called Addison’s disease).
The disease is triggered by a gene called ABCD1, which encodes a protein that resides in the membrane of an intracellular organelle called veroxisome, which is a very long chain fatty acid. Is thought to play a role in linking the vesicle to the veroxisome. Veroxisomes work by a pathway that completely degrades the very long fat-protecting acids and then passes them on to the mitochondria for complete degradation. It is thought that abnormalities in the function of the protein produced by ABCD1 cause the accumulation of very long-chain fatty acids in the cytoplasm, which is thought to cause disease, but the detailed mechanism is not yet fully understood. Has not yet been elucidated. The ABCDI gene is located at the end of the X chromosome at the end of Nagaoka called Xq28. The X and Y chromosomes, called sex chromosomes, have two X chromosomes for women and one X and Y chromosome for men. Therefore, the number of female X chromosomes is twice as large as that of males.
There is a mechanism to prevent this, and one of the X-color bodies is active per cell, similar to a male cell. This process is called X chromosome inactivation, and is known as the Ryan hypothesis proposed by British female geneticist Mary Ryan in 1961. This inactivation of the X chromosome occurs randomly, so when viewed in somatic cells as a whole, 50% of the cells inactivate the paternal X chromosome and 50% of the cells inactivate the maternal X chromosome.
However, this inactivation may occur after returning, and when a gene related to disease development has occurred in one of the X chromosomes, the normal X chromosome that has no change happens to be inactivated more often. If so, it is thought that the number of normal functioning X chromosomes will decrease, and as a result, disease may develop. Such individuals are called symptomatic carriers.
How many neurological symptoms do carrier women show in adrenal gland leukodystrophy? So far, there has been no systematic research report, but in 2014, a report was made by the University of Amsterdam in the Netherlands (1). In this report, 46 carrier reports (22-76 years old (average 48 years old)) were observed, and the main types of Korean bed symptoms were gait disorders and peripheral nerve symptoms.
Many of the neurological disorders can be understood by conducting tests such as nerve conduction tests.The main neurological symptoms are both lower-class tastes and gait disorders. Similar to symptoms, but milder than male patients. Such symptoms often appear with age, and in women with less than 40 warehouses, only 18% of those who show any symptoms, but over 60 years old, 88% of those who have any symptoms.
Comparing the impact on life function, the average of the entire group of women with symptoms is the same as the effect on life function one year after onset in Parkinson’s disease patients Is considered to be a mild gait disorder. Last year, Italy reported 11 reports of 32 carriers.
(2). Among them, 19 people show some symptoms, the main symptoms of which are, as in the above-mentioned report, leg extremity and gait disturbance. Although there is not enough information about the degree of functional impairment, one case of walking is described as severe, and many people think that the degree of impairment is mild.
It is worth noting that four of them are advocating for their support. In this way, it can be understood that even if any symptoms occur, it is often after passing the age of 40, and even in that case, it is often mild from the point of view of the store. As you can see from looking at athletes, this is the time to begin a decline in dynamic functions after the age of 40, so go out and exercise your body actively, enjoy sports, etc.
I think that such activities are important. According to my personal experience, there are many people who feel pain in the lower limbs, inability to get up in the early morning and start walking in the early morning, especially when they have not prepared and warmed up their bodies. This applies to many people, so I think that it is often easier to start moving little by little while warming up rather than suddenly starting to walk.
Regarding walking disorders, some people have wheelchairs, but I think that these numbers are limited. If you have any symptoms, it is likely that you would have a lot of trouble with lower limb tension, or lower limb pain, but if you have symptoms, it may be better to consult with a neurologist
At present, no fundamental treatment has been established for spasticity and gait disorders, and symptomatic treatment is the basis. There is a possibility that it can be alleviated by an anti-spasmodic agent, but if the drug is too effective, it may be difficult to walk, so consult with your physical condition and consult with your neurologist.
1.Engelen M, Barbier M, Dijkstra IM, et al. X-linked adrenoleukodystrophy in women: a cross-sectional cohort study.Brain 137: 693-706, 2014 2.
Natural history of a cohort of ABCD1 variant female carriers.Eur J Neurol 26: 326-332, 2019