GM1 ganglioside deposition disease is an autosomal recessive disorder with a poor prognosis.GM2 ganglioside deposition disease. The primary deficiency of acidic mono-beta galactosidase produces infantile familial nigrostriatal dementia, called GM, deposition disease. The main pathological changes are massive lipid deposits in the neuronal cells of the cerebral cortex, cell degeneration and loss of cells, and late myelin loss and glial cell proliferation. Etiology and pathogenesis of ganglioside deposition disease 1. GM1 ganglioside deposition disease GM1 ganglioside deposition disease is caused by the lack of acidic β-galactosidase in affected children, which blocks the GM1 degradation process. The function of this enzyme is to hydrolyze the galactosyl groups bound by GM1 and other galactose-containing oligosaccharide molecules, and its coding gene is located at 3p21.33. There are many mutations in the gene, so clinically there are various subtypes with very different symptoms. To facilitate clinical diagnosis, prognosis and genetic counseling, the disease is usually divided into infantile (type I), juvenile (type II) and chronic late-onset (type III) forms. Patients have accumulation of keratin sulfate and other substances in various tissues in addition to GM1. The disease is an autosomal recessive disorder with a poor prognosis. 2. GM2 ganglioside deposition disease This group of diseases is an autosomal recessive disorder due to the deficiency of β-aminohexosaminidase A, B or activator protein (GM-A). In the absence of this enzyme, N-acetylgalactose (NANA) bound to the GM2 molecule cannot be detached by hydrolysis, resulting in impaired GM2 degradation and deposition in the body. Hexosaminidase (Hex) has two isozymes, hexosaminidase A (HexA) and hexosaminidase B (HexB). Both of them can hydrolyze glycoproteins and glycolipids, but only HexA can hydrolyze GM2 gangliosides, and it depends on GM2 activator protein (GM2A gene encoding product), so mutations in any of the HexA, HexB or GM2A genes may cause defects in HexA, HexB or GM2 activator protein, thus making GM2 gangliosides degradation impaired and accumulate in cells, i.e. GM2 ganglioside deposition disorder. Both isozymes consist of two polypeptide chains: HexA has two peptide chains, α and β (α, β); HexB has two p-peptide chains (β, β). α, β chains and the gene encoding GM2A are located at 15q23-q24, 5q13 and 5q33.1, respectively. α peptide chain gene mutation results in loss of HexA activity and clinical manifestation of Tay-Sachs disease (type B). Mutations in the β peptide chain gene result in the loss of both HexA and HexB enzymatic activities, and the clinical presentation is Sandhoff disease (type O); mutations in the GM2A gene result in defective GM2 activator protein, and the presentation is AB variant. Symptoms of ganglioside deposition disease 1. GM1 ganglioside deposition disease (1) Type I (infantile type): the most serious type, most children have the disease at 3-6 months of age, and a few have the disease in the neonatal period. The initial manifestations are generalized hypotonia, poor sucking, feeding difficulties, and poor response to the outside world. Within a few months of birth, the liver and spleen are enlarged and often accompanied by an ugly face, such as a protruding forehead, large ears, low nasal bridge, gingival hyperplasia and a giant tongue. The child has delayed mental and motor development and cannot sit alone until 7 to 8 months of age; he is sensitive to sound and can jump at the slightest stimulation; he has disoriented movements and gradually develops nystagmus, paroxysmal spasms, convulsions, hyperactive tendon reflexes, posterior lumbar spine protrusion and joint ankylosis. If the child survives beyond the age of 1 year, he or she is often decerebrate and prone to recurrent respiratory infections, dying of bronchopneumonia around the age of 2 years. Specific foam cells can be found in the bone marrow, liver and spleen, and lymph nodes of the child. Skeletal X-rays often show multiple bone dysplasia, osteoporosis, acromegaly and malformation of the anterior vertebral body edges. In about 50% of children, cherry red spots can be found on fundus examination, and some patients have corneal clouding. (2) Type II (late-onset infantile type, or juvenile/adolescent type): the onset of the disease is slightly later, mostly at 12 to 18 months of age. The first symptoms are often walking instability such as abnormal gait, easy to fall, followed by unstable upper limb movements, inability to sit or stand alone, and aphasia, gradually progressing to spastic tetraplegia and common seizures. The child usually has no peripheral nerve involvement, liver or spleen enlargement, no retinal or corneal lesions, normal visual acuity and normal facial appearance. Skeletal radiographs show mild acetabular and thoracic and lumbar vertebral dysplasia and proximal metacarpal deformities. Children often die within 3 to 10 years of age due to pulmonary infection. (3) Type III (chronic late onset, adult type): Onset after 4 years of age, mostly in childhood and adolescence, but also as late as 30-40 years of age. Patients often have dysarthria and altered muscle tone as the initial symptoms, and the disease progresses slowly, up to 10 years, and intelligence may be mildly impaired, usually without ataxia, myoclonus, epilepsy and other symptoms, no facial abnormalities, liver and spleen enlargement, no retinal or corneal lesions. Mild flattening of vertebral bodies of the spine may be seen on skeletal radiographs. 2. GM2 ganglioside deposition disease Due to the variety of gene mutations, the clinical manifestations of this type of disease are highly variable. Most children are born with no obvious abnormalities, and the disease develops gradually with the increase of deposits. Depending on the age of onset, GM2 ganglioside deposits can be classified into infantile (including Tay-sachs disease, Sandhoff disease and AB variant) and late onset (including late onset infantile, juvenile and adult forms). (1) Tay-Sachs disease (TSD): This disease is also known as B-type GM2 ganglioside deposition disease (type I), which is caused by the accumulation of GM2 in neurons due to the defect of hexosaminidase alpha chain (gene locus 15q23-24), and the incidence is about 1/112000. ). (2) Sandhoff disease: This disease, also known as O-type GM2 ganglioside deposition disease (type II), is caused by mutations in the gene encoding the β-peptide chain of hexosaminidase (located at 5q13). The deficiency of HexA leads to the accumulation of GM2, which can be partially derived from salivary acyl gangliosides (GA2) by metabolic bypass of N-acetylneuraminic acid; however, since further degradation of GA2 still requires the participation of HexB, children with Sandhoff disease have both GM2 and GA2 accumulation. In addition, because the degradation of erythrocyte glycosylated lipids also depends on the hydrolysis of HexB, erythrocyte glycosylated lipids are also stored in various internal organs. The GM2 level in the brain tissue of the affected children was 100-200 times higher than normal, and the GA2 level was 50-100 times higher than normal. Erythrocyte glycosylated lipid deposits were predominant in the liver, kidney, and spleen viscera. The clinical manifestations of the disease are very similar to Tay-Sachs disease, with most of the children being normal during the first few months of life, with only more startle phenomenon, and gradually appearing around 6 months of age with reduced muscle tone, inability to sit or stand, blindness, convulsions, mild hepatomegaly and splenomegaly. The disease progresses rapidly, there is no effective treatment, and death often occurs within 2 years of age. 3, AB variant AB type is rare, the clinical manifestation is similar to Tay-Sachs disease, but the cerebellar symptoms are relatively obvious.