mucopolysaccharidosis type 1
Introduction
Introduction to mucopolysaccharidosis type I Mucopolysaccharidoses (MPS) is a group of hereditary mucopolysaccharide metabolic disorders caused by lysosomal abnormalities. It is a congenital rheumatism caused by the deficiency of enzyme activity and the accumulation of incompletely decomposed glucosamine. The common clinical features are varying degrees of epiphyseal changes, mental retardation, visceral involvement and corneal opacity; biochemical characteristics are decomposing catabolism of acid mucopolysaccharides, resulting in excessive accumulation of mucopolysaccharides in the cells, as well as excessive urine. The mucopolysaccharide is discharged. basic knowledge The proportion of illness: 0.0003% Susceptible people: no special people Mode of infection: non-infectious Complications: pulmonary hypertension, pneumonia, bronchitis, umbilical hernia, femoral hernia, retinopathy
Cause
Mucopolysaccharidosis type I cause
Cause:
The cause of this disease is autosomal recessive inheritance.
Pathogenesis
The pathogenesis of this disease is autosomal recessive inheritance. The basic defect is the lack of lysosomal aL-iduronidase, and the gene is located at 22-22q11, which causes the decomposition of mucopolysaccharide to occur, and there are various tissue cells in the body. The decomposed mucopolysaccharide deposits are excreted with urine, and the two mucopolysaccharides excreted from the urine are dermatan sulfate and heparan sulfate, both of which have iduronic acid on the side chain of the polysaccharide.
Pathology: The pathological changes of this type can be involved in almost every organ and tissue in the body. The most serious changes are found in the brain, heart, liver, spleen, brain volume, weight gain, pia mater thickening, milky turbidity. , cardiac hypertrophy, pericardium, endocardium, chordae, valve have flaky or nodular hypertrophy, coronary artery is white cord-like, can be blocked by endometrial deposition, or stenosis, hepatosplenomegaly Hard, the appearance is gray.
Microscopically, there are swollen large cells in many tissues, and there are a lot of mucopolysaccharide deposits, called Hurler cells or balloon-like cells. These cells may belong to fibroblasts, macrophages or other cells, which are found in heart valves. Tissues such as blood vessels, meninges, corneas, tendons, and periosteum, due to the dissolution of mucopolysaccharide in formalin, when stained with PAS, mucopolysaccharide deposits dissolve, hepatocytes, Kupffer cells, spleen and lymph node reticular cells, Epithelial cells of the endocrine glands, chondrocytes, bone cells and retinal cells, etc., also have mucopolysaccharide deposition, which can make the cells vacuolized. Similar to Hurler cells, the analysis of cell deposits by histochemical method proves to be mucopolysaccharide. Abnormal intracellular deposits are in the lysosome.
The neurons and glial cells of the central and peripheral nervous system are swollen with lipid-like deposits. The histochemical characteristics are the same as those of gangliosides. Electron microscopy shows that the sediments in the neurons often aggregate or form a layered structure. The zebra body is very similar to the membranous cytoplasmic body at the time of gangliosideosis.
Prevention
Mucopolysaccharidosis type I prevention
Glycogen accumulation disease is a group of children with disorders of hereditary glycogen metabolism. It is characterized by excessive accumulation of glycogen in the body tissue and difficulty in decomposition. It is rarely a metabolic disorder of glycogen, resulting in less glycogen storage in the body. The original cumulative disease is not a disease, but a group of diseases. There are 12 kinds of diseases currently identified. The clinical features are characterized by hypoglycemia. The organs involved are mainly liver, kidney and skeletal muscles. Chromosomal recessive inheritance, no gender differences, mostly in childhood, some patients to adults, the disease no longer develops, can maintain general health.
The patients are mainly due to the lack of certain enzymes that break down glycogen, such as glucose-6-phosphatase, -1,4 glucose chymase, phosphofructokinase, hepatic phosphorylation kinase and the like.
Parents of many patients marry close relatives, avoiding close relatives marriage is an important part of preventing this disease. Once glycogen accumulation is found, it is mainly to prevent and treat hypoglycemia, a small amount of meals, limit fat and total calories, limit physical activity, serum lactic acid The highest, should take sodium bicarbonate to prevent acidosis, corticosteroids, adrenaline, glucagon, etc. can help control hypoglycemia.
Complication
Mucopolysaccharidosis type I complications Complications pulmonary hypertension pneumonia bronchitis umbilical hernia retinopathy
1. The nervous system can be complicated by spasticity.
2. The circulatory system can be complicated by cardiac hypertrophy, pulmonary hypertension, and extensive coronary infarction, which can cause sudden death.
3. The respiratory system can be complicated by ventilatory disorders, pneumonia and bronchitis.
4. The digestive system can be complicated by hepatosplenomegaly, sometimes with umbilical hernia or femoral hernia.
5. The facial features may be accompanied by prominent eyeballs or retinal lesions, conductive deafness, which may be due to ossicular deformity.
Symptom
Mucopolysaccharidosis type I symptoms Common symptoms Nasal flat collapsed gums Hypertrophy Lip thick tongue Large liver splenomegaly Mental retardation Lysosome enzyme deficiency cartilage dysplasia with... Increased hair eye widening rough skin
The symptoms of visceral lesions, skeletal deformities and mental retardation are very serious. The appearance of the child is normal at the time of birth, but it can quickly show the backwardness of exercise and mental development. It can be clearly revealed when the age is 1 to 2 years old. The characteristics of the disease, the child's appearance gradually becomes rough, the nose is wide and flat, the eye distance is wide, the lip is thick, the tongue is large, the ear is low, the teeth are small and sparse, the gums are thick, the skin is thick, the hair is increased, the eyebrows are long, the head is long. Increased circumference, sagittal suture early closure, anterior and posterior diameter increase (scapular head), occasional hydrocephalus, severe deformity of bones and joints, short and short fingers, short neck, back bend of the spine, gradually shrinking and straightening of each joint, finger fixation In the semi-flexion position, it is claw-shaped and short.
Nervous system
Mainly due to low intelligence, it is obvious after 1 year old, the action is stupid, the language is backward, and the response to the surrounding environment is slow. The degree of mental retardation is related to the concentration of mucopolysaccharide in the cerebrospinal fluid. There are not many authors of convulsions, other neurological signs, If the phlegm reflex is reduced or hyperthyroidism, sputum sputum, pathological reflexes, etc. may also occur.
2. Circulatory system
Cardiovascular symptoms are obvious, may have cardiac hypertrophy, pulmonary hypertension and systolic murmur of the left sternal or apical apex caused by valvular disease, extensive coronary infarction, can cause sudden death.
3. Respiratory system
Repeated respiratory infections, ventilatory disorders, increased secretion of nasopharyngeal, tonsil and adenoid proliferation, craniofacial deformity, can cause narrowing of the nasopharyngeal cavity, difficulty breathing, mouth breathing, voice, if the thoracic deformity is accompanied Bronchial cartilage deformity, it is more difficult to breathe, and is prone to pneumonia and bronchitis.
4. Digestive system
Most patients have abdominal bulging, hepatosplenomegaly, smooth and hard, is an important feature of this disease, sometimes with umbilical hernia or femoral hernia.
5. Five senses
Visual acuity and hearing are also abnormal. The cornea changes from foggy to severe turbidity. Later, it can develop to blindness. Some have large corneas, prominent eyeballs or retinal lesions, and conductive deafness, which may be caused by ossicular deformity.
Examine
Mucopolysaccharid storage disease type I examination
Excessive dermatan sulfate and heparan sulfate appear in the urine, and metachromatic mucopolysaccharide particles (Reilly body) appear in leukocytes and bone marrow cells in the blood.
X-ray inspection
(1) Limb bone: due to excessive deposition of mucopolysaccharides in the bone, abnormal osteogenesis and chondrogenic activity, mainly in the tubular bone to cause bone formation and contraction and shortening, early bone thickening, cortical thickening, medullary stenosis In the late stage, the cortex becomes thinner, the medullary cavity is widened, and one or both ends of the backbone become thinner, often with a slow-growing end. This change is obvious in the upper limbs compared to the lower limbs, the upper limbs are thick and short, and the middle part is bulging, two The end is thinner, which is one of the characteristic changes of the disease. The proximal end of the humerus is varus deformed. Due to the asymmetric growth of the two ends of the diaphysis, the bone end can be bent and tilted, especially at the distal end of the ulna. The surface is relatively inclined, the proximal end of the femur often becomes thin and curved, which can form obvious hip varus deformity, and some can be hip valgus deformity. The distal femur is lightly or inversely extended. The short tube bone is short and the metacarpal bone is near. The end is contracted, sharpened, conical, the distal end of the phalanx is usually small, the distal phalanx is dysplastic, the ossification is incomplete, and when the metacarpal has these changes, the humerus often becomes slender.
(2) Torso: Lumbar 1 or lumbar 2 vertebral body dysplasia, smaller and backward displacement, seems to be squeezed out, the spine also protrudes backward from the center and appears as an angular deformity, the front of the vertebral body The upper part of the margin is absent, and the lower part is herringbone. It is distinct from the tongue-like protrusion in the middle of the type IV vertebral body of the mucopolysaccharidosis. The bulging of the other vertebral bodies is approximately circular, and the posterior margin of the lumbar vertebral body is often inwardly concave. The roots are slender, the osteoporosis is loose, the humeral wing is deployed outward, the humerus is poorly developed and narrowed, the acetabular angle is enlarged, the ribs are widened, the spine ends are thinned, and the shape is like a paddle, and the inside of the clavicle is widened. The outer side is tapered and has a "hook" shape.
(3) The skull: often increased, with hydrocephalus as the common type. In most cases, the saddle is enlarged, mainly due to the increase of anteroposterior diameter, which is in the shape of B, which is caused by the deformity of the sella, and the closure of the cardia is slow. The forehead and the edge of the eyelid are prominent, the eyes are separated too far, the mandible is underdeveloped, but the angle is increased.
2. Determination of microenzyme activity
Dimethylmethan-Tris (DMB-Tris method) is used for the detection of glycosaminoglycans (GAGs) in urine and the determination of GAGs in amniotic fluid. The former is mostly used for screening or diagnosis of children, while the latter is used for production. Pre-diagnosis.
3. Genetic diagnosis
The gene locus 22-22q11 can be diagnosed early by RFLP or PCR.
Diagnosis
Identification of mucopolysaccharidosis type I diagnosis
According to the special clinical manifestations of this type, combined with family history, pathological changes and related laboratory tests, the diagnosis can be confirmed.
However, it is necessary to carefully identify with other types of mucopolysaccharidosis, especially the type IV of polysaccharide storage, and the achondroplasia is carefully identified.
