Niemann-pick's disease

　　This disease is an autosomal recessive inheritance, and Jews are more susceptible. It has been confirmed that the types A and B of this disease are caused by the lack of sphingomyelinase. This enzyme is widely present in the lysosomes of various tissue cells, and is also found in mitochondria and microsomes, especially in liver cells. Sphingomyelin exists in the cell membrane and subcellular membrane of all cells, including the matrix of red blood cells. When this enzyme is lacking, these lipids cannot be hydrolyzed, causing them to accumulate in large quantities inside the cells, and they are often accompanied by the deposition of cholesterol and bisphosphates. The mechanism of cholesterol increase is unclear, and there seems to be a close relationship between cholesterol and sphingomyelin metabolism, and there may also be a small increase in other myelin lipids.

　　In patients with type C and D, the main deposits are cholesterol, less sphingomyelin, and sphingomyelinase levels are also reduced in the cells, and the levels are between types A, B, and normal people. Exogenous cholesterol esterification (esterification) is significantly impaired in the fibroblasts of the patient's skin, and based on this possible pathogenesis, pure homozygous, carrier, and prenatal diagnostic methods have been established, therefore, it is considered to be the pathogenic cause of this type.

　　The gene of sphingomyelinase is located on chromosome 17, and its structure is clear. The gene mutation of type C is on chromosome 18.

　　Patients may develop the disease in infancy,表现为内脏病变缓慢进展，the onset of nervous system lesions is later, or appear adult onset with only visceral lesions. Infection is a common complication and the main cause of death, active treatment should be given.

　　This disease is a common disease in the infant and toddler period, generally normal at birth, symptoms appear within 6 months after birth, early symptoms include loss of appetite, vomiting, diarrhea, malnutrition, and significant weight loss. Patients have pale complexion, yellowish skin, and may also have brownish pigmentation. Physical and motor development are delayed, intelligence gradually declines, and becomes like an idiot. Some cases may have symptoms such as deafness, blindness, paralysis, and even rigidity, tremors, and seizures. Physical examination shows liver and spleen enlargement, up to 10 cm below the rib, with a relatively hard texture. Lymph nodes may also slightly enlarge. About 1/3 of cases show cherry red spots in the macula of the fundus examination, which is completely the same as that seen in familial idiocy. Anemia is generally not severe, early white blood cell count is high, and there is a relative increase in lymphocytes. Large vacuoles can be seen in the cytoplasm of lymphocytes and monocytes. In the late stage, platelets may decrease, serum neutral fat increases, phospholipids are normal, cholesterol is normal or slightly high, and liver function is generally normal or slightly poor. Clinically, there are mainly 3 types, and some literature reports that it can be divided into 5 types.

　　1. Acute infantile type (Type A):This type accounts for more than 85% of Niemann-Pick cases, with most cells in the body lacking sphingolipase, and clinical symptoms of liver, spleen, and lymph node enlargement and neurological damage. Half of the patients have cherry-red spots around the macula of the fundus. This type has a rapid progression of the disease, and most patients die of severe消耗 and infection within 3 years.

　　2. Chronic visceral type (Type B):Onset in infancy and childhood, characterized by growth retardation, slow progression of the disease, most patients die in their teens or early adulthood, with liver, spleen, and lymph node enlargement, sometimes accompanied by splenic hyperfunction, and generally without neurological manifestations.

　　3. Type C:All manifestations of this type can occur. Some patients without sphingolipase deficiency may develop slowly progressive visceral lesions in infancy, with the onset of neurological lesions later, or may present with adult-onset disease accompanied only by visceral lesions.

　　Same as preventive measures for genetic diseases, avoid consanguineous marriage, do a good job of genetic counseling, and measuring the enzyme activity of skin fibroblasts can detect hemizygotes of types A and B. Culturing amniotic fluid cells for enzyme activity detection can be used for prenatal diagnosis of types A and B. If a child already has this disease, there is a 50% chance that the fetus carried later may also have the disease. Therefore, prenatal enzyme activity testing should be performed on the fetus, and induced abortion may be necessary if necessary.

　　1. Blood picture

　　Moderate anemia and thrombocytopenia may be present, the degree of which depends on the extent of bone marrow involvement. White blood cells are generally normal, but may decrease or even slightly increase. Lymphocytes and monocytes may have vacuoles.

　　2. Bone marrow image

　　The degree of bone marrow hyperplasia and the proportion of various cells are normal. Typical Niemann-Pick cells can be found, which have a diameter of 20-90μm and are round, elliptical, or triangular. They contain a small, eccentric nucleus and the cytoplasm is filled with foam-like myelin phospholipid granules resembling mulberry-like fat droplets. This structure makes the cytoplasm appear foamy, hence also known as foam cells. They appear pale blue under Wright's stain, positive for lipid (Sudan III) staining, and the wall of the vacuole is positive for glycogen staining, while the center is negative. Staining for alkaline phosphatase and peroxidase is negative.

　　3. X-ray examination

　　Type A may have granulomatous infiltration in the lungs, mild medullary expansion and thinning of the bone cortex, and changes in gray matter, demyelinating lesions, and cerebellar atrophy can be seen in brain CT and MRI examinations.

　　4. Enzyme determination

　　White blood cells, skin biopsy fibroblast culture determination of sphingomyelinase are all reduced.

　　5. Renal biopsy

　　Under light microscopy, the renal tubular epithelial cells, the wall layer of the glomerulus, and the visceral epithelial cells all show foamy degeneration. Under the electron microscope, some renal tubular epithelial cells show zebra bodies, and some show atypical concentric arrangement.

　　6. Other

　　Under light microscopy, the renal tubular epithelial cells, the wall layer of the glomerulus, and the visceral epithelial cells all show foamy degeneration. Under the electron microscope, some renal tubular epithelial cells show zebra bodies, and some show atypical concentric arrangement.

　　1. Dietary regimen for Niemann-Pick disease

　　Eat a balanced diet, eat more fruits and vegetables and other high-fiber foods, eat more eggs, soybeans and other high-protein foods, pay attention to a light diet, and engage in moderate exercise.

　　2. What food should be avoided if there is a deficiency of phosphatidylcholine cholesterol transferase

　　Avoid smoking, alcohol, spicy, coffee and other irritant foods.

　　Currently, there is still no specific radical curative treatment. The main treatment is supportive and symptomatic treatment, pay attention to nutrition, low-fat diet can be adopted. Clinical symptoms can be treated symptomatically, and nursing care should be strengthened.

　　At present, there is no effective treatment method for this disease.

　　Firstly, general treatment

　　Mainly for symptomatic treatment, strengthen nutrition. Control the intake of diet.

　　Secondly, drug treatment:

　　1. Use antioxidants such as vitamins.

　　2. E or styrylbutene can prevent the oxidation and polymerization of unsaturated fatty acids contained in the myelin phospholipid M, reduce the formation of lipofuscin and free radicals.

　　3. C type children can try dimethyl sulfoxide.

　　4. Gene recombinase replacement therapy for A, B type children is under study.

　　5. Resection: Suitable for non-neurotype, with hyperplasia of splenic function. However, the impact on the patient after splenectomy should be considered.

　　6. There have been successful reports on fetal liver transplantation.