What Is the Relationship Between Tay-Sachs and Genetics?

Refers to a recessive autosomal genetic disease related to sphingomyelin metabolism. Lack of lipoenzyme hexose deaminase A results in accumulation and precipitation of cortical and cerebellar nerve cells and ganglioside GM2 in axons.

Tay-sachs

Refers to a recessive autosomal genetic disease related to sphingolipid metabolism. Cortical and cerebellar nerves are caused by the lack of lipoglucanase hexose deaminase A

Refers to a recessive autosomal genetic disease related to sphingomyelin metabolism. Lack of lipoenzyme hexose deaminase A results in accumulation and precipitation of cortical and cerebellar nerve cells and ganglioside GM2 in axons. Retinal neurofibrosis exposes the veins and veins in the macular area, and ophthalmoscopic examination can reveal diagnostic pink spots. Within 6 months after birth, there may also be severe intellectual and psychomotor developmental disorders, irritability, blindness, tonic convulsions, convulsions, and eventually denervation of the brain and death around 3 years old. The disease has the highest incidence among Ashkenazi Jews. In recent years, the incidence of heterozygote screening and prenatal diagnosis has decreased. Same as: GM2 Ganglioside deposition There are other aliases for this disease, please refer to the following information:
Chinese name: Ganglioside deposition disease English name: gangliosidosis
Alias: Systemic ganglioside disease; Ganglioside deposition disease; Black-faced idiot; Pseudo-Hurler disease; Tay-Sachs disease; Sandhoff disease

-galactosidase gangliosidosis is caused by the lack of acidic -galactosidase in children, which blocks the degradation of GM1. The function of this enzyme is to hydrolyze the galactosyl group bound by GMI and other galactose-containing oligosaccharide molecules. Gangliosides are widely present in various cells of the human body, with the highest levels in brain and nerve tissue. Human brain contains at least 10 kinds of gangliosides with different structures, GM1 is the most important one. The degradation of GM1 must be carried out gradually in the lysosome through a series of hydrolytic enzymes. Defects in any of these enzymes will cause the deposition of gangliosides in the lysosome, and then damage the cells and organs, namely gangliosides. The main clinical manifestations of lipidosis are central nervous system symptoms.

-galactosidase gangliosidosis is a group of autosomal recessive genetic diseases, which is a significant deficiency of B-galactosidase, and A, B, and c isoenzymes have defects. As a result, monosialic acid tetrahexosyl ganglioside, GM (1), is deposited in the central nervous system and various other internal organs.

Pathogenesis Principle The lack of different enzymes in the ganglioside hydrolysis metabolism causes the deposition of different substances in the nervous tissue and causes the disease. Gangliosides are glucolipids composed of ceramide combined with an oligosaccharide molecule and sialicacid, and are distributed on the nerve cell membrane of nerve tissue.
The primary lack of acidic -galactosidase causes the first step of the above decomposition process to fail and the deposition of monosialceramide tetrahexoside in neurons, resulting in infantile familial scotopic dementia, called GM1 Patients with this type of deposit have severe cerebellar damage, and degeneration of the myelin sheath of the retinal degeneration spinal cord and peripheral nerves to varying degrees. The lack of aminohexidase causes the above-mentioned second step decomposition failure and the deposition of monosialceramide trihexosides in neural tissues to produce GM2 deposition disease. Among them, type is infant type, which is called Tay-Sachs disease, type is acute early infant type, called Sandhoff disease. The main pathological changes are a large amount of lipid deposits in nerve cells in the cerebral cortex, degeneration and disappearance of late myelin sheath loss and glial cell proliferation. Electron microscopy showed that the deposits had a circular layered structure, called membranous cytoplasm. Except for the involvement of the brain, the cerebellum and the brainstem have atrophy and the ventricles are enlarged.

Clinical Symptoms 1. The clinical manifestations of GM1 ganglioside deposition disease can be divided into type and type , also known as systemic ganglioside disease and pseudo-Hurler disease. Appearances are specific: convex forehead, concave nose, low ears, huge tongue Gingival hyperplasia, human features, corneal opacities, joint contractures, liver and splenomegaly, and cherry red spots in the macular area of the fundus. Facial edema in the frog-shaped position during the neonatal period, poor mental development due to poor lactation. At 6 to 7 months, the child still had no response to the periphery, weakness in swallowing, inability to reduce the tension of the erector muscles, reduced voluntary activity, and hypertenoid reflexes. The auditory allergy scares reflexes are very obvious. Convulsions frequently occur. Anticonvulsant medications are often ineffective. As the course of the disease progresses, the decortical tonic state rarely survives beyond 2 years of age.
People with type are generally normal in appearance during the neonatal period, but they have obvious auditory allergies and shock reflexes. Frequent systemic convulsions, myoclonic seizures, and retarded development may be associated with mild hepatosplenomegaly within 6 months, and there is no cherry red in the macular area of the fundus. Point 2. The clinical manifestations of GM2 ganglioside deposition disease are caused by aminohexidase deficiency, of which type is infant type, which is typical of Tay-Sachs disease; type is acute early infant type called Sandhoff disease.
Patients with Tay-Sachs disease begin to show reduced attention to their surroundings 4 to 6 months after birth. Normal exercise reduces muscle tone, reduces auditory allergy, startle, screaming myoclonus, or involuntary laughter may be the first early manifestations. Within 3 to 4 months after the onset of disease, the course of the disease develops rapidly, head circumference increases, vision gradually decreases, and black and gradual appearance of optic nerve atrophy. Physical examination shows poor pupillary light response, small liver and spleen, and more than 90% of children can see fundus macular cherry red After the age of 1 year, the body muscle tension increased, and the cortical tonic-angled arched posture was reversed, and the patient was screaming in pain, but he couldn't make a sound. After 2 years of age, he was completely demented, and the frequent myoclonic and convulsive reactions disappeared. Sucking and swallowing ability disappeared. Instead, nasal feeding is required. The average course of disease is about 2 years. Most children die before the age of 3 to 4 years.
Sandhoff's disease is similar to Tay-Sachs' disease, but the former is accompanied by hepatosplenomegaly and progresses more rapidly. Type patients have late onset and are characterized by progressive psychomotor decline. Brain, liver, spleen, and kidney have GM2 deposits. But to a lesser degree, progress is slower and can range from 10 to 15 years.

The special appearance and clinical symptoms of galactosidase diagnosis can provide reference for diagnosis. Cherry red spots in the macular area of the fundus are common signs, but they can also be found in Nimann-Pick disease and Gaucher disease without characteristic significance.
X-rays show abnormal thickness distribution of cortical bone in long bones of vertebral dysplasia. Wedge metacarpal wedge-shaped saddle-shaped ribs and laminar sacral flank can provide evidence for diagnosis. About 50% of peripheral blood lymphocytes have vacuoles and bone marrow tissue cells. Hollow vesicle formation can support diagnosis.
The artificial substrate to determine the enzyme activity of -galactosidase and aminohexosidase in serum and skin fibroblasts is the only way to diagnose ganglioside deposition disease and further typing. Note that it is distinguished from other common hereditary neurological diseases such as sphingomyelinosis, infantile Gaucher disease, and galberocerebrosidelipid disease Farber's disease.

Skin fibroblast inspection laboratory inspection 1. Determine the enzyme activity of -galactosidase and aminohexosidase in serum and skin fibroblasts.
2. Vesicle formation in peripheral blood lymphocytes.
Other auxiliary examination blood lymphocyte examination 1. Void formation in bone marrow tissue cells.
2. X-ray examination of vertebrae dysplasia, abnormal distribution of thick bone cortex in long bones, metacarpal wedge-shaped saddle shoe-shaped, ribbed lamellar, sacral ectasia, etc.
There is no special treatment for this disease, which can be treated symptomatically in the clinic to prolong the survival of children. Enzyme supplementation is still being studied.
The prevention of selective abortion has a very poor prognosis. GM1 gangliosideosis type I rarely survives over 2 years of age. GM2 ganglioside deposition disease has an average duration of about two years. Patients with type have a late onset and can live up to the age of 10 to 15 years. It is difficult to treat genetic metabolic diseases, and prevention of dissatisfaction is even more important. Preventive measures include the avoidance of marriage between close relatives, the introduction of genetic counselling, carrier genetic testing and prenatal diagnosis and selective abortion to prevent the birth of children