Niemann-Pick disease

Introduction to Niemann-Pick disease Niemann-pick's disease (NPD) is an inherited metabolic disease caused by sphingomyelin and cholesterol deposited in various organs of the body. It is often seen in young children. It has liver and spleen and yellow spots on the fundus. The main features of large red foam spots and large foam-like cells in bone marrow smears. basic knowledge The proportion of sickness: 0.01% Susceptible people: young children Mode of infection: non-infectious Complications: hypersplenism

The cause of Niemann-Pick disease

(1) Causes of the disease

Autosomal recessive inheritance.

(two) pathogenesis

The disease is autosomal recessive, and Jewish people are more ill. It is now confirmed that the A and B strains of this disease are caused by the lack of sphingomyelinase, which is widely present in lysosomes of various tissue cells, mitochondria. Also found in microsomes, especially in hepatocytes, sphingomyelin is present in the plasma membrane of all cells and sub-plasma of the cells, including the matrix of red blood cells. When the enzyme is deficient, such lipids cannot be hydrolyzed, resulting in cells. A large amount of accumulation, often accompanied by the deposition of cholesterol and bisphosphonate, the principle of increased cholesterol is not clear, cholesterol and sphingomyelin metabolism seems to be closely related, there may be a small increase in other nerve sheath lipids.

In the cells of type C and type D patients, the main deposits are cholesterol, sphingomyelin is less, and the sphingomyelinase in the cells is also decreased. The level is between A and B and normal people, and is found in the skin fibroblasts of patients. Esterification of source cholesterol has obvious obstacles, and based on this possible pathogenesis, homozygotes, carriers and prenatal diagnosis methods have been established, and this is considered to be the cause of this type.

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

Niemann-Pick disease prevention

If a child has a disease for this disease, 50% of the fetuses in the future may have the disease. Therefore, the fetus should be tested for prenatal enzyme activity and if necessary, abortion should be performed.

Niemann-Pick disease complications Complications, hypersplenism

Infection is a common complication and a major cause of death and should be treated aggressively.

Symptoms of Niemann-Pick disease Common symptoms Loss of appetite, loss of weight, eating, vomiting, tremor, dry skin, yellowish gait, unstable learning, hepatosplenomegaly, infant feeding difficulties, cherry erythema

The disease is a common disease in infants and young children. It is usually normal at birth, and symptoms appear within 6 months after birth. The early manifestations are loss of appetite, vomiting, diarrhea, low nutrition and obvious weight loss. The patient is pale and the skin is waxy yellow. Brownish yellow pigmentation, physical and motor development are slow, intelligence gradually declines, become an idiot-like, in some cases can have symptoms such as deafness, blindness, paralysis, limb stiffness, tremors, and even convulsions, physical examination with liver and spleen parallel swelling Large, up to 10cm under the ribs, the texture is hard, the lymph nodes can be slightly enlarged, about 1/3 of the cases have a cherry red spot on the macula, which is exactly the same as that seen by the black cockroach family idiot; anemia is generally not Heavy, early white blood cells are higher, lymphocytes are relatively increased, and large vacuoles are seen in the cytoplasm of lymphocytes and monocytes; late platelets can be reduced, serum neutral fat is increased, neurophospholipids are normal, and cholesterol is normal or slightly higher. Liver function is generally normal or slightly poor; there are mainly three types in clinical practice, and some literature reports that they are classified into five types.

1. Acute infant type (type A) This type accounts for more than 85% of Nie-mann-Pick cases. Most cells in the body lack sphingosporate, clinically appear liver, spleen, lymphadenopathy and nervous system damage symptoms, half of patients Sakura red spots appear around the macula of the fundus. This type of disease develops rapidly and dies in severe consumption and infection within 3 years.

2. Chronic visceral type (type B) occurs in infancy and childhood, showing growth retardation, slow progression, most patients die in their teens or just entering adulthood, liver, spleen, swollen lymph nodes, sometimes with spleen function Hyperthyroidism, generally no neurological manifestations.

3. All manifestations of type C can occur. Some patients have no sphingosine phosphatase deficiency. Patients can develop slow-developing visceral lesions in infancy, neurological lesions appear later, or appear in adulthood. There are visceral lesions.

Niemann-Pick disease check

Blood picture

There may be moderate anemia, thrombocytopenia, the extent of which depends on the extent of bone marrow involvement, white blood cells are generally normal, can be reduced or even slightly increased, lymphocytes and monocytes may have vacuoles.

2. Bone marrow

The degree of myeloproliferation and the proportion of various cells are normal. Typical Niemann-Pick cells can be found. The cells are 20-90 m in diameter, round, elliptical or triangular, with a core with a small eccentricity and a cytoplasm filled with foam. The sphingomyelin granules resemble mulberry-like fat droplets. This structure makes the cytoplasm foamy, so it is also called foam cells. The Ritter staining is light blue, the lipid (Sudan III) staining is positive, and the glycogen staining vacuoles. The wall was positive, the vacuole center was negative, and alkaline phosphatase and peroxidase staining were negative.

Other auxiliary inspections:

X-ray examination

Type A patients may have miliary infiltration in the lungs. The bone may have mild medullary enlargement and cortical thinning. Brain CT and MRI may have gray matter degeneration, demyelinating lesions and cerebellar atrophy.

2. Enzyme assay

White blood cells, skin biopsy fibroblast cultures were measured to reduce sphingomyelinase.

3. Renal biopsy

Under light microscopy, renal tubular epithelial cells, glomerular wall layer and visceral epithelial cells were foamy degeneration. Under electron microscope, renal tubular epithelial cells were zebra bodies, and some were atypical concentric circles.

4. Other

Skin fibroblast culture detects cholesterol esterification, has a disorder in type C, and is also stained with filipin, which shows accumulation of unesterified cholesterol in lysosomes. Rectal biopsy before neurological symptoms appear (sometimes Years can clearly show the deposition in C-type nerve cells.

Diagnosis and differentiation of Niemann-Pick disease

diagnosis

Infants and young children have liver, splenomegaly, and the liver is larger than the spleen, and the nervous system appears gradually. The disease should be suspected. If there is a cherry red spot in the macular area, there are miliary changes in the lung X-ray film to support the disease. Diagnosis, the important diagnosis is based on the discovery of typical foam-like Niemann-Pick cells in the bone marrow, and the determination of sphingomyelinase activity can be confirmed if reduced.

Differential diagnosis

It should be identified with the following diseases:

Glycogen storage disease

There are eight types of glycogen storage disease. The most common types are type I, II, III and IV. The liver is large and the spleen is generally small. Type I is more common in 1 year old and has repeated episodes of hypoglycemia. The mental retardation is caused, the child's body shape is also short, and the fat accumulation in the cheeks is a baby face, which is different from the neurological symptoms and physical development of Niemann-Pick disease. Types III and IV are similar to type I, but Light, Ia can still affect the heart, can be identified by clinical manifestations, glucose tolerance curve or glucagon test and Niemann-Pick disease.

2. Gaucher disease

Gossip cells were found in bone marrow puncture or spleen puncture smear, -glucocerebrosidase activity was decreased, and serum alkaline acid phosphonase was increased.

3. GM1 ganglioside storage disease

Fucosidosis storage disease has liver, splenomegaly and mental retardation. The former has foam cells in the bone marrow and red spots on the macula, but both have ugly faces and bone dysplasia in bone X-ray films. which performed.

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