CM1 gangliosidosis
Introduction
Introduction to CM1 ganglioside storage disease CM1gangliosidosis is a hereditary lysosomal disease caused by -galactosidase deficiency. Its genetic pattern is autosomal recessive, and its clinical features are progressive central nervous system. Barriers and skeletal abnormalities similar to mucopolysaccharidosis type I. basic knowledge The proportion of illness: 0.00035% Susceptible people: no specific people Mode of infection: non-infectious Complications: respiratory infections
Cause
Causes of CM1 ganglioside storage disease
(1) Causes of the disease
Genetic defects, the apparent lack of three acidic -galactosidase isoenzymes A, B and C in the body of the body is the main cause of the disease.
(two) pathogenesis
Histochemical and biochemical studies have shown that CM1 ganglioside storage disease is caused by the apparent lack of three acidic -galactosidase isoenzymes A, B and C in various tissues of the body, which can be divided into I, II. Type III, type IV, the pathogenesis and pathological changes are mainly type I and type II. There is a significant deficiency of -galactosidase in type I children. When the activity of the enzyme is decreased, CM1 gangliosides are deposited in the body. In the organs, especially in the gray matter, in addition, the enzyme is also involved in the degradation of certain acidic mucopolysaccharides, so that partially degraded acidic mucopolysaccharides are deposited in the tissue cells, of which the most obvious in the liver cells are deposited in the body. Gangliosides may be derived from the cell membrane of various cells, because there are a large number of gangliosides in this structure, and the type II CM1 ganglioside storage disease is also a -galactosidase deficiency, but its pH activity curve The isozyme type differs from the type I.
Pathology: Under the microscope, the pathological change of type I is that all organ tissues have balloon-like vacuoles, which are most obvious in cells and neurons of reticuloendothelial system. Histochemical staining of cytoplasmic inclusions shows glycolipid in lysosomes. In sedimentation, the substances deposited in neurons are strongly sultanate and PAS weakly positive, while the histochemical staining of glial cells and visceral cells mainly shows the characteristics of polysaccharides in hepatocytes, Kupffer cells, and glomerular cells. , renal tubular epithelial cells, tissue cells, reticulocytes of hematopoietic tissue, cardiomyocytes, epithelial cells, connective tissue cells of the lungs and intestines, large lysosomes are visible, examined by electron microscopy, with membrane empty The bubble contains fine amorphous, slightly hydrophilic substances, and occasionally contains a layered film structure.
In the brain, cerebellum, brainstem, spinal cord and autonomic ganglion cells, neurons are balloon-like under the microscope, which is caused by a large number of lysosomes with a membrane structure. In addition, there is still a gelatin in the brain tissue. Reaction and demyelination changes, similarly, mononuclear cells in the surrounding blood, cultured skin fibroblasts, under the microscope can have cytoplasmic inclusion bodies, the inclusion body, toluidine blue staining is heterochromatic, in the electron Under the microscope, the two cells showed an increase in lysosomes, which contained transparent particulate matter.
Biochemical analysis of neurons deposited in the body, mainly composed of CM1 gangliosides and monoterpenic acid derivatives, cholesterol, a small amount of phospholipids and glucose sphingomyelin, visceral inclusion bodies deposits mainly from glycoproteins and monoterpenic acid Mucopolysaccharide and a small amount of CM1 gangliosides.
The pathological changes of type II are similar to those of type I, but to a lesser extent. The internal organs can be free of CM1 ganglioside deposition, but there is mucopolysaccharide deposition, and excessive mucopolysaccharide can be excreted in the urine. Neuronal sediment CM1 in the brain. Cerebrosides are also lower than type I.
Prevention
CM1 ganglioside storage disease prevention
Carry out marriage and birth guidance, strive to reduce the incidence of genetic diseases in the population, and improve the quality of the population.
Complication
Complications of CM1 ganglioside storage disease Complications, respiratory infections
Type I patients can have lumbar vertebrae changes, there are cherry red spots on the macula of the fundus, as well as hepatosplenomegaly and multiple bone dysplasia, thickening of the skin, sometimes telangiectasia, type II often die of repeated convulsions and respiratory tract Infection, some patients with type III may have diffuse vascular keratomas and reduced muscle tone.
Symptom
CM1 ganglioside storage symptoms Symptoms Symptoms tachycardia expression indifferent reflexes into the short-neck spleen hepatosplenomegaly in the fundus macular part of the cherry... Stupid gait instability is slow
1. Type I, also known as systemic ganglioside storage disease, also known as infant type, is characterized by:
(1) Severe brain degeneration, more than 2 years of age.
(2) Storage of gangliosides in neurons, liver, spleen and other tissue cells and glomerular epithelial cells.
(3) Skeletal deformities showing Hurler's disease.
The disease begins early, usually at the time of birth, symptoms of mental and motor disorders can occur, the child's appearance is severely abnormal, showing a rough face like Hurler syndrome, the forehead is prominent, the bridge of the nose is flat, the distance between the eyes is widened, the gums are thick, and the tongue is extended. Short neck and hirsutism, most cases have no corneal opacity, but all patients have lumbar vertebrae changes and yellow spots on the fundus macular, as well as hepatosplenomegaly and multiple bone dysplasia, thickening of the skin, sometimes capillary Vasodilatation, frog shape in the neonatal period, mental development is low, until 6 to 7 months, the response is slow, can not follow the object, and even no response to the outside world, muscle tension is reduced, spontaneous movement is less, sputum reflex is active, The onset of convulsions is a prominent symptom, and it appears earlier. Ineffective treatment with antispasmodic drugs, convulsions, repeated respiratory infections and paroxysmal tachycardia are the main causes of death in children before the age of 2 years.
2. Type II is also known as juvenile type. It is late onset, and the neonatal period is generally normal. At 1 year of age, mental, motor and neurological symptoms such as ataxia, gait instability, uncoordinated movement, and convulsion occur. , language barriers, indifferent expressions, dull eyes and hyperreflexia, and can gradually deteriorate with the development of the disease, type II in addition to the onset of late, there is a longer course of disease, older age, no bones clinically Abnormal, no Hurler syndrome-like face, no hepatosplenomegaly, no yellow spots on the fundus, no visible red spots, visual acuity and hearing are usually not damaged, mostly died in 3 to 5 years old, often died of repeated convulsions and respiratory infections.
3. Type III is also known as adult type, Reuser et al. classify type IV into adult type, this type is late onset, and some patients may have mild systemic ganglioside storage symptoms at the age of 20 years old. After the onset of progressive mental retardation, slurred speech, cerebellar dysfunction and vision loss, mild spinal changes, no hepatosplenomegaly and cherry red spots on the fundus macular, some patients may have diffuse vascular keratinoma, reduced muscle tone When the patient is lying down or sitting relaxed, the abnormal posture of muscle tension and abnormal movement of muscle tone do not disappear. Magnetic resonance imaging shows that the lenticular nucleus has high-density lesions with bilateral symmetry.
Examine
Examination of CM1 ganglioside storage disease
In the blood around the type I patients, lymphocytes, monocytes, and cultured skin fibroblasts can be seen with intracellular vacuoles, but the positive rate of type II patients is low, and type I patients may have excessive glycoproteins in the urine. Type II patients can excrete excessive acid mucopolysaccharide in the urine, biochemical analysis of skin fibroblasts and liver tissue, and CM1 gangliosides and keratan sulfate deposition can be seen.
The earliest X-ray of type I showed long tubular bone, new bone formation of rib periosteum, followed by vertebral dysplasia, and a bird's beak. The thoracolumbar scoliosis, the ribs became thinner at the vertebral body, and the rest were ships. Paddle-like, there may also be a "B" shaped saddle, the humeral wing is flared outward, the metacarpal deformity, the claw-like hand, the joint is stiff, the elbow joint and the knee joint are flexed and contracted, and the skeletal deformity is not obvious in the neonatal period. It is more pronounced at 5 to 6 months. Most patients with type II have no skeletal abnormalities, and even mild symptoms of skeletal abnormalities.
Diagnosis
Diagnosis and identification of CM1 ganglioside storage disease
Diagnosis can be obtained based on clinical symptoms, pathological features and laboratory tests.
Type I needs to be differentiated from certain mucopolysaccharidosis, but the latter has a longer course. Types II and III should be differentiated from infants with CM2 ganglioside storage disease. The latter is not affected, and can be passed if necessary. The enzyme was measured to further confirm the diagnosis.
