What Is Neuronal Ceroid Lipofuscinosis?

With the study of histochemistry, enzymology and molecular biology of pathological tissues, there is a growing understanding of genetic diseases caused by lipid metabolism disorders. Lipidosis is a group of lipid metabolism disorders that cause lipids. Hereditary disease caused by cytoplasmic deposition in cells in the body. Different metabolites caused by the deficiency of different enzymes during the degradation of sphingomyelin are deposited in tissues, resulting in different clinical symptoms and different diseases. The neuropathy caused by lipidoid disease can be roughly classified into three situations:

Sphingomyelinosis

Sphingomyelinosis (sphingomyelinosis), also known as Niemann-Pick disease, is a genetic metabolic disease caused by sphingomyelinase deficiency. It is an autosomal recessive gene located at 11p15v. It is characterized by full monocytes and the nervous system with a large number of foam cells containing sphingomyelin. Higher Snow's disease is rare. It is an autosomal recessive inheritance, and it is more common in Jews, and its incidence is as high as 1/25 million. There are currently at least five types.

Overview of sphingomyelinosis

1. Lipid-like deposition diseases that mainly damage white matter, such as heterochromic white matter dystrophy and globular white matter dystrophy (Krabbe disease). The common features of this group of diseases are demyelination of the white matter and abnormal deposition of lipids in systemic tissues. Another group of Sudan-staining white matter dystrophy includes Schilder's disease Pelizaeus-Merzbacher disease. Although the lack of enzymes is unknown, but also It is a hereditary disease.

2. Lipid-like deposition diseases involving both white matter and gray matter, such as Nimann-Pick disease, Gaucher disease is characterized by severe deposition of lipids in the brain and viscera. There are swelling vacuoles of neurons in the brain and extensive plaque myelination. Hepatosplenic lymph nodes and bone marrow have a large amount of lipid deposits that cause organ enlargement and bone marrow dysfunction.

3. Grey matter lipid deposition diseases, GM1GM2, GM3 lipid deposition diseases belong to this category. In pathology, lipid deposition in a wide range of neurons, swelling and disappearance of ganglion cells, and subsequent secondary demyelination. Clinically, convulsions, abnormal startle reflexes, myoclonic convulsions, and decreased intelligence are the common features of this group of diseases.

Causes of sphingomyelin deposition

This disease is an autosomal recessive hereditary disease. The disease is caused by the lack of sphingomyelinase, which causes the sphingomyelin metabolism disorder, which causes the latter to accumulate in the monocyte macrophage system and cause hepatosplenomegaly and central nervous system degeneration. change. Sphingomyelin is formed by the connection of N-acysphingosine and a molecule of phosphocholine at the C site. Sphingomyelin is derived from various cell membranes and erythrocyte matrix and is swallowed by macrophages during the process of cellular metabolism and aging. Rear.

The activity of this enzyme is highest in normal liver. The liver, kidney, brain, and small intestine are also rich in this enzyme. The activity of enzymes in liver and spleen of patients with this disease is reduced to less than%. After the enzyme is deficient, systemic sphingomyelin metabolism is disrupted. -In the macrophage system and nervous tissue cells.

Pathogenesis of sphingomyelinosis

Sphingomyelin is one of the components of sphingomyelin and other cell membranes. It is hydrolyzed to ceramide and phosphorylcholine under the action of sphingomyelinase. Due to the lack of this enzyme or the activity is reduced, sphingomyelin is incompletely hydrolyzed and deposited in tissue Internal swelling, degeneration, and foam cell formation of cells, that is, where sphingomyelin deposition disease cells invade can cause visceral swollen nerve cells to die, myelin loss, and so on. The main pathological change is that specific foam cells with a diameter of 20 90 & micro; m can be seen in the rich internal organs of the reticular endothelial system, such as liver, spleen, bone marrow, kidney and lung tissue. Typical infantile or subacute juvenile patients may have severe neurological damage, with cerebellar brainstem and spinal cord involvement being more pronounced, and cerebral cortex milder. Lipid deposition in neurons or nucleus (such as dentate nucleus) causes a significant reduction in neurons, astrocytes or glial cells hyperplasia, normal white matter in the brain, or severe myelinated changes in the brain.

Clinical manifestations of sphingomyelinosis

According to the age of onset and the presence or absence of neurological symptoms, the disease can be divided into 5 types:

1. Typical infants (acute infants) are the most common. Often within 3 months of the birth of the baby, irritable progressive hepatosplenomegaly, lymphadenopathy, weight loss, vomiting, jaundice, anemia exercise, and mental retardation. On physical examination, the whole body muscles were reduced, tendon reflexes were weakened, and intelligence was low. There were cherry red spots on the macular area of the fundus; and blindness, deafness, swallowing difficulties, generalized convulsions, spastic paralysis, and pathological reflexes. Children often die within 2 to 4 years of age from hypersplenism, liver failure, and recurrent infections. A very small number of cases are relatively stable after onset and can live to about 10 years of age. 2. Visceral infant type (chronic visceral type) This type of child has normal growth and development except liver and spleen, without neurological signs and mental retardation.

3. Juvenile (subacute juvenile) onset is relatively common, and symptoms often appear as gait instability and ataxia at the age of 1 to 6 years. Later hepatosplenomegaly, decreased muscle tone, abnormal tendon reflexes, etc. A few years later, the neurological symptoms of hypointelligence gradually manifested as symptoms and signs such as convulsions, spastic gait disorders, susceptibility to panic, and urinary incontinence. Some patients may have supraoptic manifestations of supranuclear ophthalmoplegia and progressive mental decline.

4. The symptoms of the New Scottish family variant of this disease show neurological manifestations, behavioral decline, mental retardation, epileptic seizures, and ataxia in children.

5. Adult-type non-neurological symptoms are mainly manifested by hepatosplenomegaly.

Complications of sphingomyelinosis

This disease is often accompanied by liver failure, hypersplenism, and infections such as systemic and pulmonary infections, which are more common in typical infants.

Diagnosis of sphingomyelinosis

Liver, splenomegaly, and mental retardation in newborns or children. Patients with ataxia should consider the possibility of this disease. Foam cells seen in bone marrow smears have important reference diagnostic value. Peripheral blood leukocytes and nerve sheaths in tissue cultured fibroblast The determination of phospholipase activity is of specific diagnostic significance and should be distinguished from liver disease and hypersplenism.

Diagnosis basis of sphingomyelinosis

hepatosplenomegaly; with or without nervous system damage or cherry erythema; vacuoles in peripheral blood lymphocytes and monocyte cytoplasm; foam cells can be found in bone marrow; lungs are miliform or reticulate Infiltration; sphingomyelinase activity can be measured under conditions, confirmed by sphingomyelin excretion, liver, spleen or lymph node biopsy. More common in infants less than 2 years old, but also in the neonatal period. The main symptoms are hepatosplenomegaly, anemia, malnutrition and stunting in the longer course. Some may have deafness, convulsions, myotonia, and hypotonia. Niemann-Pick cells can be confirmed in bone marrow. Its five types are as follows:

1. Acute neurotype (type A or infant) is a typical Niemann-Pick (85%), mostly within 3 to 6 months after birth, and a few cases develop within a few weeks or after 1 year of life. The first is loss of appetite, vomiting, difficulty in feeding, extreme wasting, dry and yellowish skin, progressive mental retardation, hypokinesia, hypotonic paralysis, and eventually idiots. Half have cherryredspot, blindness, jaundice and liver. Spleen. Anemia and cachexia mostly died before the age of 4 due to infection. Skin often has small yellow nodular rashes and deafness. The sphingomyelin accumulation is 20 to 60 times the normal, the enzyme activity is 5 to 10% of the normal, and the minimum is <1%. 2. Non-nervous type (-type or visceral type) Infants or children can see the disease in their childhood, the disease progress is slow, and the liver and spleen are enlarged. Normal intelligence, no neurological symptoms. Can live to adults. The cumulative amount of SM is 3 to 20 times normal, and the enzyme activity is 5 to 20% of normal. The lower is the same as type A.

3, juvenile (C-type chronic neurotype) more common in children, a small number of young children or adolescents. Postnatal development is more normal, and a few have early jaundice. Hepatosplenomegaly is often the first episode, and most of them develop neurological symptoms at the age of 5 to 7 (also early or late in adolescence). Intellectual decline, language barriers, learning difficulties, emotional changes, gait instability, ataxia, tremor, hypertonicity and tendon reflex, convulsions, dementia, cherry erythema or supranuclear vertical eye paralysis. Can live to 5 to 20 years old, individual can live to 30 years old. The cumulative amount of SM is 8 times normal, and the enzyme activity is up to 50% of normal, which can also be close to normal or normal.

4. Nova-scotia type (D type) The clinical process is slower than the juvenile type, with obvious jaundice, hepatosplenomegaly, and neurological symptoms, more than school-age death, and reduced enzyme activity.

5. Adult adults develop symptoms, normal intelligence, no neurological symptoms, and liver and splenomegaly with varying degrees. Can survive for a long time. The cumulative amount of SM is 4-6 times normal, and the enzyme activity is normal.

Sphingomyelinosis disease test

Laboratory inspection

1. Peripheral blood marrow cytology smears can find foam cells. 2. Leukocyte bone marrow culture and liver, spleen, lung, and rectal biopsies such as sphingomyelate increased, while sphingomyelinase activity decreased or lacked.

Other auxiliary inspections

Measurement of type 1 to 2 prenatal amniotic fluid. The decrease in sphingomyelinase activity in fibroblast culture is of great significance for prenatal diagnosis.

Sphingomyelinosis treatment

The disease can only be treated symptomatically, such as liver protection, anti-seizure control, and so on.

1. Antioxidants Vitamin C, E or stilbene can prevent the peroxidation and aggregation of unsaturated fatty acids contained in sphingomyelin M and reduce the formation of lipofuscin and free radicals.

2. Splenectomy is suitable for non-neuropathy and hypersplenism.

3. Embryo liver transplantation has been successfully reported.

Prevention of sphingomyelinosis

Typical infants often die of hypersplenism, liver failure, and repeated infections within the age of 2 to 4 years. All types may be complicated by liver failure, hypersplenism, and infection. Genetic counseling is often performed. Preventive measures include avoiding genetic testing, prenatal diagnosis, and selective abortion of close relatives and marriage carriers to prevent child birth. The disease is often autosomal recessive, and most patients marry for close relatives of their parents. According to this situation, the incidence of this disease can be reduced from the perspective of strengthening the strict implementation of the "prohibition of marriage of close relatives" to effectively improve the people in China physical fitness.