ganglioside deposition disease
Introduction
Introduction to ganglioside deposition disease Gangliosidosis is a group of autosomal recessive hereditary diseases. The lack of different enzymes in ganglioside hydrolysis and metabolism causes the deposition of different substances in nerve tissue and cause disease. basic knowledge Sickness ratio: 0.0001% Susceptible people: no special people Mode of infection: non-infectious Complications: epilepsy
Cause
Causes of ganglioside deposition
Cause:
As a group of autosomal recessive hereditary diseases, it is a significant defect of -galactosidase, and all kinds of isozymes of A, B and C are defective, resulting in tetradecanoyl ganglioside monophosphate (GM1). ) deposited in the central nervous system and other internal organs.
Pathogenesis
The lack of different enzymes in the kinetic metabolism of gangliosides causes the deposition of different substances in the nervous tissues and causes disease. Ganglioside is a glycolipid composed of a combination of ceramide and an oligosaccharide molecule and sialic acid, which is distributed on the nerve cell membrane of nerve tissue.
The primary deficiency of acid -galactosidase causes the first step of the above decomposition process to fail and the deposition of mono-camphoramide tetrahexosides in neurons, resulting in infantile familial black montmorillonosis, called GM1 Sedimentary disease This type of patients have severe cerebellar damage, and the retinal degeneration spinal cord and peripheral nerves have different degrees of myelin loss. The lack of hexosaminidase causes the above-mentioned decomposition of step 2 to produce GM2 deposition disease in the deposition of nerve tissue with mono-camphoramide trihexosides. Type I is an infant type, and the type of Tay-Sachs disease type II is an acute early infant type called Sandhoff disease. The main pathological changes are a large number of lipid deposits in the nerve cells of the cerebral cortex. Cell degeneration, loss of myelin in the late stage of disappearance and glial cell hyperplasia can be seen as a circular layered structure, called membranous cytoplasm. In addition to brain involvement, the cerebellum and brainstem are generally atrophied and enlarged.
Prevention
Ganglioside deposition prevention
Genetic metabolic diseases are difficult to treat, and the efficacy is not satisfactory. Prevention is more important. Preventive measures include avoiding close relatives, conducting genetic counseling, genetic testing of carriers, prenatal diagnosis and selective abortion to prevent the birth of children. In daily life, we should pay attention to nutrition and rationality. Try to diversify foods as much as possible. Eat high-protein, multi-vitamins, low-fat animal fats, digestible foods, fresh fruits and vegetables, and do not eat old-fashioned or irritating things. Grilled, marinated, fried, salty foods, staple foods and coarse grains to ensure nutritional balance. To achieve a moderate amount of food per meal, 3 meals a day, to the specified time, regardless of hungry or hungry, should take the initiative to eat, to avoid hunger or fullness.
Complication
Gangliosideosis complications Complications
As the disease progresses, the clinical symptoms and signs are diverse, especially the combined mental retardation, blindness, epilepsy, lung infection, and falls.
Symptom
Symptoms of ganglioside deposition disease Common symptoms Corneal opacity myoclonus weakness, reflexes, hypertonic muscle tension, joint contracture, kyphosis, optic atrophy, decoction, dementia
1. Clinical manifestations of GM1 ganglioside deposition disease: It can be divided into type I and type II.
Type I is also known as systemic gangliosideosis, pseudoHurler disease, and the appearance of the child is specific: convex forehead, concave nose, low ear, huge tongue, gingival hyperplasia, special length of human, corneal opacity, joint contracture, liver, spleen Large, yellow spot on the fundus has cherry red spots, frog shape in the neonatal period, facial edema, poor breastfeeding, and poor mental development. At 6 to 7 months, the child still has no response to the outside, swallowing weakness, not vertical. Reduced muscle tone, reduced autonomic activity, hyperreflexia, hypersensitivity, shock and reflexes, frequent seizures, anticonvulsant medications are often ineffective, with the progression of the disease, gradually appear cortical tonic state, rarely live 2 years old.
Type II is generally normal in the neonatal period, normal appearance, but hypersensitivity, scare reflex is obvious, often within 6 months of systemic convulsions, myoclonic seizures, developmental backwards, etc., may be associated with mild liver, splenomegaly, no fundus Red spots in the yellow spot area.
2. Clinical manifestations of GM2 ganglioside deposition disease: caused by aminohexosaminidase deficiency, of which type I is infant type, that is, typical Tay-Sachs disease; type II is acute early infant type called Sandhoff disease.
Patients with Tay-Sachs disease, normal at birth, begin to reduce attention around the body 4 to 6 months after birth, reduce exercise, reduce muscle tone, hearing allergies, startle, scream, myoclonus episodes or involuntary laughter For the early performance of the first episode, the disease course develops rapidly within 3 to 4 months after onset, the head circumference increases, the visual acuity decreases and the occultation gradually appears. The optic nerve atrophy, the physical examination shows that the pupillary light response is poor, the liver and spleen are not large, more than 90% The child can see the red spot on the fundus macular cherry. After 1 year old, the muscle tension of the limb is increased. The cortical tonic anterior horn is reversed, the pain is screaming, but the sound is not loud. After 2 years old, the whole body is demented. With seizures, the reaction disappeared, the sucking and swallowing ability disappeared and nasal feeding was required. The average course of disease was about 2 years, and most of the children died before 3 to 4 years old.
Sandhoff's disease is similar to Tay-Sachs' disease, but the former is characterized by liver, splenomegaly and more rapid progression. Type II patients have late onset, characterized by progressive spirit and motor decline, brain, liver, spleen and kidney. There are GM2 deposits inside, but to a lesser extent, so the progress is slower and can live to 10 to 15 years old.
Special appearance and clinical symptoms can provide a reference for diagnosis. The red spot on the fundus macular area is a common sign, but it can also be seen in Nimann-Pick disease and Gaucher disease without characteristic significance.
Examine
Examination of ganglioside deposition disease
1. Determination of the related enzyme activities of -galactosidase and hexosaminidase in serum and dermal fibroblasts.
2. There are vacuoles in the surrounding blood lymphocytes.
3. There are vacuoles in the bone marrow tissue cells.
4. X-ray examination of vertebral dysplasia, abnormal distribution of thick cortical bone in long bones, metacarpal wedge shape, saddle shoe shape, rib bone shape, humerus external and so on.
Diagnosis
Diagnosis and differentiation of ganglioside deposition
Diagnostic criteria
X-ray shows vertebral dysplasia, abnormal distribution of cortical thickness in long bones, wedge shape of the metacarpal, shoe-shoe shape, rib flaky shape, external iliac bone, etc. can provide evidence for diagnosis, about 50% of peripheral blood lymphocytes are available Bubbles, formation of hollow cells in bone marrow tissue cells, etc. can support diagnosis.
Artificial Substrate Determination of the related enzyme activities of -galactosidase and hexosaminidase in serum and dermal fibroblasts is the only method for diagnosing gangliosideosis and further typing.
Differential diagnosis
Pay attention to the identification of common hereditary nervous system diseases such as sphingomyelinosis, infantile Gaucher disease, galactocerebrolipidosis, and Farber disease.
