I. Overview Niemann-Pick disease (NPD for short), also known as sphingomyelin lipidosis, is a congenital glycolipid metabolic disease. It is characterized by a large number of foamy cells containing neurosphingomyelin in all mononuclear macrophages and in the nervous system. It is less common than Gaucher’s disease. It is autosomal recessive and has a high Jewish prevalence of 1/25,000. there are at least five types. Diagnosis: ①hepatosplenomegaly; ②with or without neurological damage or cherry erythema of the fundus; ③vacuolation of peripheral blood lymphocytes and monocyte plasma; ④bone marrow foam cells can be found; ⑤x-ray lungs show corn-like or reticulocytic infiltrates; ⑥the condition can be confirmed by nerve sheath phospholipase activity measurement, nerve sheath phospholipid excretion, liver, spleen or lymph node biopsy. There is no special treatment, but symptomatic treatment is the main focus, with fat diet and nutrition. 1.Antioxidants Vitamin C, E or butyl hydroxystilbene can prevent the peroxidation and aggregation of unsaturated fatty acids contained in nerve sheath phospholipids M, and reduce the formation of lipofuscin and free radicals. 2.Splenectomy Suitable for non-neurological type with hypersplenism. Embryonic liver transplantation has been reported to be successful. The disease is caused by the deficiency of sphingomyelinase, which leads to the impaired metabolism of sphingomyelin. The latter accumulates in the mononuclear macrophage system, resulting in hepatomegaly, splenomegaly, and degeneration of the central nervous system. Nerve sphingolipids are composed of N-acyl sphingomyelin linked to a molecule of phosphocholine at the C1 site. Neurosphingolipids are derived from various cell membranes and the erythrocyte matrix, among others. After being phagocytosed by macrophages during cellular metabolic aging. This enzyme is most active in the normal liver and is also abundant in the liver, kidneys, and small intestine of the brain. In patients with this disease, the activity of the enzyme is reduced to less than 50% in liver and spleen tissues. In 1914, Niëmann reported a case in which the patient died at 18 months of age, and in 1934, it was discovered that the disease was a neurophosphatidosis, but it was not until 1966 that it was recognized to be due to a deficiency of sphingomyelinase. In the absence of this enzyme, the systemic neurosphingomyelin metabolism is disturbed, and neurosphingomyelin is deposited in the monocyte-macrophage system and neural tissue cells. Clinical manifestations Most often seen in infants and children under 2 years of age, but also in the neonatal period. 1. Acute neurological type (type A or infantile type) is typical of Niemann-Pick (85% of cases), mostly in the first 3-6 months of life, with a few onset in the first few weeks or after 1 year of life. Initially, the disease is characterized by loss of appetite, vomiting, feeding difficulties, extreme emaciation, dry, waxy yellow skin, progressive mental and motor decompensation, hypotonia and floppy paralysis, eventually becoming an idiot, half of them have cherryred spot of the fundus, blindness, jaundice with hepatosplenomegaly. Anemia, cachexia, and death before 4 years of age due to infection. The skin often shows a small yellow verrucous rash with deafness. The accumulation of neurospherin is 20-60 times higher than normal, and the enzyme activity is 5-10% of normal, with a minimum of <1%. 2, non-neurological type (beta type or visceral type) Infancy or childhood hair open the door to see the mountain, the course of the disease is slow to progress, hepatosplenomegaly prominent. Normal intelligence, no neurological symptoms. SM accumulation is 3-20 times higher than normal, enzyme activity is 5-20% of normal, low as in type A. 3. Juvenile type (C chronic neurological type) Most often seen in children, a few young children or adolescents. Postnatal development is mostly normal, and a few have early jaundice. Hepatosplenomegaly is often the first sign, and most of the neurological symptoms appear at the age of 5 to 7 years (may be earlier or later in adolescence). They include mental retardation, language impairment, learning difficulties, emotional changes, gait instability, ataxia, tremor, hypertonia and tendon reflexes, convulsions, dementia, and cherry erythema or supranuclear vertical oculomotor paresis seen in the fundus. SM accumulation is 8 times higher than normal, and enzyme activity is up to 50% of normal, or close to normal or normal. 4.Nova-scotia type (D type) has a slower clinical course than the juvenile type, with marked jaundice, hepatosplenomegaly, and neurological symptoms, and most deaths occur at school age, with reduced enzyme activity. 5, Adult type Adult onset, normal intelligence, no neurological symptoms, varying degrees of hepatosplenomegaly. SM accumulation is 4-6 times normal and enzyme activity is normal. 6. Auxiliary tests 1. Blood picture: normal hemoglobin or mild anemia; leukocytopenia when hypersplenism is apparent. Monocytes and lymphocytes often show characteristic vacuoles, about 8 to 10, which have diagnostic value. These vacuoles are lipid-filled lysosomes on electron microscopy. The platelet count is normal, with advanced hypersplenism and decreased time to significant bone marrow invasion. The patient's leukocytes lack neurophospholipase activity. 2. Bone marrow picture: contains typical Niemann-Pick cells, often called foam cells, with nuclei 20-100 μm in diameter; nuclei are small, round or ovoid, usually single, or may be binucleated; cytoplasm is abundant, filled with round drop-shaped clear vesicles, resembling mulberry-like or foamy. The electron microscopy showed that the vesicles were surrounded by a partial membrane layer structure. Examination of unstained specimens with a bitemporal microscope showed small bubble-like cells in the cytoplasm, unlike Gaucher cells. Under polarized light, the vesicles are birefringent; under ultraviolet light, the fluorescence is greenish-yellowish. Biochemical characteristics PAS reaction is weakly positive, the wall of the vesicles in the cytoplasm is positive, the center of the vesicles is negative; acid phosphatase, alkaline phosphatase, Sudan black are negative reaction. 3, plasma cholesterol, total lipids may be elevated, SGPT mildly elevated. 4. Urinary excretion of neurosphingomyelin is significantly increased. 5, liver, spleen and lymph node biopsies have heaped, patchy or diffuse foam cell infiltration. Neurospherin. In long-term surviving cases, due to the proliferation of lipid-filled histiocytes in the skeleton, there may be osteoporosis, widening of the medullary cavity, thinning of the bone cortex, and even focal areas of destruction in the long bones, but there is no skeletal expansion deformity change. After infancy, the alveoli are infiltrated by lipid-filled histiocytes, and lung manifestations similar to histiocytic hyperplasia X are seen. In conclusion, it is non-specific and only provides a basis for auxiliary diagnosis. 7. Determination of leukocyte or cultured fibroblast sphingomyelinase activity, the activity of each type of enzyme is different. 7, differential diagnosis 1, Gaucher disease infant type: predominantly large liver, hypertonia, spasticity, no fundus cherry erythema, lymphocyte plasma without vacuoles, elevated serum acid phosphatase, Gaucher cells found in the bone marrow. 2, Wolman's disease: no fundus cherry erythema, X-ray abdominal plain film can be seen in both adrenal glands enlarged, unchanged shape, with diffuse punctate calcification shadow. The lymphocytes have vacuoles in the cytoplasm. 3, GM gangliosidosis type I: born with features of appearance, high forehead, low nasal bridge, coarse skin, 50% of cases with fundus cherry erythema and lymphocyte cytoplasm with vacuoles. x-ray can see multiple bone dysplasia, especially vertebrae. 4, Hurler disease (mucopolysaccharide type I): large liver and spleen, poor intelligence, lymphocyte cytoplasm with vacuoles, bone marrow with foam cells, etc. resembling NPD. heart defect, multiple bone dysplasia, no lung infiltration. Increased urinary mucopolysaccharide excretion, neutrophils with peculiar granules. shape after 6 months, skeletal changes are obvious, vision is diminished, corneal clouding.