Pediatric Niemann-Pick disease
Introduction
Introduction to Niemann-Pick disease in children Niemann-Pickdisease (NPD), also known as sphingomyelinosis, is a congenital glycolipid metabolic disease. It is characterized by a large number of foam cells containing sphingomyelin in the whole body mononuclear macrophages and nervous system, and the main features of liver, splenomegaly and central nervous system involvement. basic knowledge The proportion of illness: the incidence rate is about 0.001% Susceptible people: children Mode of infection: non-infectious Complications: cirrhosis, ascites, hypersplenism, ataxia
Cause
The cause of Niemann-Pick disease in children
(1) Causes of the disease
This condition is a congenital disorder of glucose and lipid metabolism, which is characterized by a large number of foam cells containing sphingomyelin in the whole body reticuloendothelial system.
(two) pathogenesis
This symptom is an autosomal recessive hereditary disease. About 1/3 of the cases have a clear family history. Due to the lack of sphingomyelin deficiency, the sphingomyelin metabolism disorder causes the dysfunction of lipids and coenzymes, causing lipidoids to pass through the body. Multiple deposition, in the reticuloendothelial system, liver, splenomegaly, central nervous system degeneration, sphingomyelin is composed of N-acyl nitrosamine and a molecule of phosphorylcholine at the C1 site, nerve Sphingomyelinase is derived from various cell membranes and erythrocyte matrices. After being phagocytosed by macrophages during cellular metabolic senescence, it is hydrolyzed by sphingomyelinase to N-acyl sphingosine and phosphocholine, which is the enzyme in normal liver. The vitality is the highest, the spleen, kidney, brain and small intestine are reduced to less than 50%. The disease is divided into 6 types, and the children are mainly A, B and C.
Type A and type B are caused by ASM gene mutation, which reduces the ASM activity. The sphingomyelin and other lipids are stored in the mononuclear macrophage system. The ASM-based immobilization is located at 11p15.1~p15.4, and 12 mutations have been found. type.
The type C is a defect in the transport of exogenous cholesterol by the cells and the accumulation of unlipidated cholesterol in the lysosome. The molecular defects of this type are still unclear. In the liver and spleen of the patient, the storage is not fatified. In addition to cholesterol, there are sphingomyelin, phospholipids and glycolipids, while the brain tissue contains only glycolipids. ASM activity in leukocytes is normal. Only in cultured cells, there may be partial sphingomyelin deficiency, which is described as secondary. The accumulation of cholesterol in lysosomes, foam-like cells and navy tissue cells can be seen in many tissues. These cells are not C-specific cells, but may not be present in some cases without organ enlargement. Skin and conjunctival biopsy Specific inclusion bodies can be seen.
Prevention
Niemann-Pick disease prevention
Avoid the marriage of close relatives, do a good job in the consultation of hereditary diseases, determine the enzyme activity of skin fibroblasts can detect the A and B type hemizygotes, culture amniotic fluid cell enzyme activity test can be used for prenatal diagnosis of type A, B.
Complication
Pediatric Niemann-Pick disease complications Complications cirrhosis, ascites, hypersplenism, ataxia
Hepatic spleen lymphadenopathy and chronic lung disease, pulmonary heart disease, convulsions, growth retardation, can lead to cirrhosis, liver failure, portal hypertension and ascites, development of hypersplenism, complete cytopenia, progressive ataxia , dystonia and dementia, accompanied by repeated lung infections, mental disorders can occur during puberty.
Symptom
Symptoms of Niemann-Pick disease in children Symptoms of growth Slow growth, mental retardation, learning difficulties, fundus, erythema, loss of appetite, liver splenomegaly, language development retardation, abnormal cellular enzyme activity, peripheral hemolymph... tremor
1. Type A: Hepatosplenomegaly occurs within 6 months of birth, followed by rapid progression of the central nervous system. Early neurological manifestations of low muscle tone and muscle weakness are reflected in feeding difficulties, lymphadenopathy and pulmonary infiltration. The skin is yellow-brown and horrified. Half of the children have cherry erythema in the macular area of the fundus. They often have growth retardation, respiratory tract complications, more than 2 to 3 years of age death, and acid sphingomyelinase activity is less than 5% of normal.
2. Type B: The most common, the condition is lighter than A type. In early childhood, there is liver spleen and abdomen bulging. In severe cases, liver involvement can lead to cirrhosis, portal hypertension and ascites, and splenomegaly can develop into hypersplenism. Hematocytopenia should be done partial or total splenectomy. The splenomegaly of the mild patients can be found in the talented person. In the patient's X-ray chest radiograph, diffuse reticular posterior nodular infiltration can be seen. Severe patients can cause chronic lungs. Disease, pulmonary heart disease, most patients have no nervous system involvement, normal intelligence, there are also reports of mental retardation, life can live to adults, acid sphingomyelinase activity is 5% to 10% of normal.
3. Type C: Diversified clinical manifestations, typical manifestations of varying degrees of hepatosplenomegaly in childhood, vertical supranuclear ophthalmoplegia and slow progression of central nervous system degeneration (progressive ataxia, dystonia And dementia), vertical supranuclear ophthalmoplegia is a sign of nervous system brain stem involvement, is a characteristic sign, children with abnormal behavior in kindergarten and elementary school, often considered stupid, gradually dementia, dysarthria Difficulty in language, drooling, and dystonia are first manifested in abnormal postures of the hands and feet when walking or running, easy to wrestle, gradually becoming systemic, often accompanied by convulsions, and mental disorders can occur during puberty.
4. Other variants: Fatal neonatal liver disease, liver failure, early progressive neurological damage in infants with or without liver involvement, and adult with psychosis or progressive dementia.
Examine
Pediatric Niemann-Pick disease examination
1. Blood picture: Hemoglobin is normal or has mild anemia; leukocytes decrease when spleen is obvious, and monocytes and lymphocytes often show characteristic vacuoles, about 8 to 10, which have diagnostic value (Fig. 1). The vesicles are filled with lipid lysosomes, and the number of platelets is normal. When the spleen and bone marrow are significantly invaded in the late stage, the leukocytes are deficient in neurolipidase activity.
2. Bone marrow: Contains typical Niemann-Pick cells, often called foam cells, which are 20-100 m in diameter; small in size, round or oval, usually single or dinuclear; cytoplasm rich, It is filled with round droplets of transparent vesicles, similar to mulberry-like or foamy. Under electron microscope, some membrane layers are surrounded by vesicles. Examination of unstained specimens by phase microscope shows that the cytoplasm of the cells is vesicular, The Geshe cells are different. Under the polarized light, the vesicles are birefringent; the fluorescence is greenish yellow under ultraviolet light, the biochemical characteristic PAS reaction is weakly positive, the vesicle wall is positive in the cytoplasm, and the vesicle center is negative; acid phosphatase Alkaline phosphatase, peroxidase, and Sudan black were all negative.
3. Blood biochemical examination: Cholesterol, total fat can be increased, SGPT is slightly elevated.
4. Urine examination: The amount of sphingomyelin excreted is significantly increased.
5. Liver, spleen and lymph node biopsy: There are piles of foam cells infiltrating into pieces or diffuse sphingomyelin.
6. Determination of sphingomyelinase activity: Leukocyte or cultured fibroblast sphingomyelinase activity, different types of enzyme activity, the most reliable diagnosis.
7. X-ray examination: no characteristic X-ray findings, in long-term survival cases, due to the massive proliferation of fat-filled tissue cells in the bone can show osteoporosis, medullary cavity widening, cortical bone thinning, and even long bones can appear focal Sexually disrupted areas, but no bone swelling and deformity changes.
After infancy, the alveoli are infiltrated by fat-filled tissue cells, and the lungs are similar to those of histiocytosis X. The lungs are miliary or reticular infiltration. In short, there is no specificity, and only the basis for assisted diagnosis is provided.
8. B-ultrasound: visible liver, spleen, swollen lymph nodes.
9. EEG: There are abnormal brain waves.
10. Fundus examination: visible cherry erythema.
Diagnosis
Diagnosis and diagnosis of Niemann-Pick disease in children
diagnosis
Diagnose based on:
1. Hepatosplenomegaly.
2. With or without neurological damage or erythema of the fundus cherry.
3. Peripheral blood lymphocytes and monocyte cytoplasm have vacuoles.
4. The bone marrow can find foam cells.
5. X-ray lungs are miliary or reticular infiltration.
6. Conditional determination of sphingomyelinase activity, urinary sphingomyelin excretion and liver, spleen or lymph node biopsy confirmed.
Differential diagnosis
1. Gaucher disease infant type is mainly liver, hypertonic muscle hyperthyroidism, sputum, no fundus cherry erythema, lymphocyte cytoplasm without vacuolization, elevated serum acid phosphatase, found Goscher cells in the bone marrow.
2. Wolman's disease has no fundus cherry erythema. The X-ray abdominal plain film shows double adrenal gland enlargement, the shape is unchanged, there is diffuse punctate calcification shadow, and the lymphocyte cytoplasm has vacuoles.
3. GM gangliosidosis type I is characterized by appearance, high forehead, low nasal bridge, thick skin, 50% of cases have fundus cherry erythema and lymphocyte cytoplasm with vacuoles, X-ray visible multiple bone dysplasia Especially the vertebrae.
4.Hurler disease (mucopolysaccharide type I) Liver and spleen, poor intelligence, lymphocytic cytoplasm with vacuoles, bone marrow with foam cells and other similar NPD, heart defects, multiple bone dysplasia, no lung infiltration, urinary mucopolysaccharide Increased, neutrophils have special particles, shape after 6 months, bone changes, vision loss, corneal opacity.
