White matter genetic genes

In fact, many people don’t know much about white matter. If I were to introduce to you some relevant knowledge about white matter today, many of you might not be very interested in reading it. Because of the large number of professional terms, it is very difficult for many friends to understand. Today, we will introduce to you the genetic genes of white matter. We hope that through our introduction, we can help you understand the heredity of white matter.

Metachromatic leukodystrophy (MLD) is an autosomal recessive hereditary disease and a common type of leukodystrophy. This disease, also known as metachromatic leukoencephalopathy, is a serious neurodegenerative metabolic disease and the most common lysosomal disease.

Due to the deficiency of arylsulphatase A (ARSA) or sphingolipid activator protein B (SAP-B, saposin B), namely sulfatide activating protein, the hydrolysis of sulfatide in lysosomes is blocked, and sulfatide is deposited in the white matter of the central nervous system, peripheral nerves, and visceral tissues such as the kidneys, gallbladder, and liver, causing a progressive, degenerative neurological disease with demyelination of the white matter of the brain and peripheral nerves.

Pathogenesis

ARSA is localized at 22q13.3. ARSA gene mutation reduces the synthesis rate and stability of ARSA, thereby weakening its catalytic activity; SAP-B gene mutation causes structural changes, reducing its stability and almost completely losing its function. Both can lead to impaired hydrolysis of sulfatide in lysosomes, resulting in its deposition in the white matter of the brain, peripheral nerves and other visceral tissues. The mechanism by which sulfatide causes demyelination is still unclear. Its accumulation in oligodendrocytes and Schwann cells may inhibit the formation of myelin and promote the progression of demyelination. Other mechanisms include the myelin instability theory and the sphingosine poisoning theory.

Pathophysiology

The lesions may involve the white matter, peripheral nerves, renal collecting ducts, hepatic ducts, gallbladder, retinal ganglion cells, cerebellum, and brainstem. Some nerve nuclei of the basal ganglia, with the white matter of the brain and the renal collecting ducts being the most severely affected. The brain may appear slightly atrophied, the white matter is gray with a clear boundary between it and the gray matter, and the other organs appear normal to the naked eye. Under the light microscope, the white matter and peripheral nerves of the brain show demyelination, and a large number of phagocytes are seen; periodic acid-Schiff-positive substances can be seen in paraffin sections; when frozen sections are stained with the alkaline dye toluidine blue, a metachromatic substance that is not purple-blue but brown-red can be seen. This substance is sulfatide, from which MLD gets its name. Under the electron microscope, metachromatic substances are mainly deposited in oligodendrocytes, astrocytes, Schwann cells and renal collecting duct endothelial cells, presenting a herringbone or honeycomb lamellar structure.