Mucopolysaccharide metabolism disorder
Introduction
Introduction to mucopolysaccharide metabolic disorders The metabolic disorder of mucopolysaccharide is a disease caused by mutation of the hydrolyzing enzyme which degrades the mucopolysaccharide in the lysosome of human cells, resulting in loss of activity, mucopolysaccharide cannot be degraded and metabolized, and finally accumulated in the body. The disease is a very important class in lysosomal storage diseases, and can be divided into seven types, namely, I, II, III, IV, VI, VII, IX, among which III is further divided into IIIA, IIIB, IIIC, IIID. Four subtypes, type IV are divided into IVA and IVB subtypes. Although the pathogenic genes and clinical manifestations are different, they are collectively referred to as mucopolysaccharide metabolic barriers because the storage substrates are mucopolysaccharides. basic knowledge The proportion of illness: 0.005% Susceptible people: no special people Mode of infection: non-infectious Complications: deafness, arteriosclerosis
Cause
Causes of mucopolysaccharide metabolic disorders
Cause:
Mucopolysaccharide is a long-chain complex sugar molecule formed by a disaccharide unit composed of hexuronic acid and aminohexose or neutral sugar, which can be linked to a protein to form a proteoglycan, which is a connective tissue matrix. An important component of mitochondria, nuclear membrane, plasma membrane, etc. Mucopolysaccharide can be deposited on any part of the body, such as connective tissue deposited under the skin, which can cause rough face, stiff skin, limited mouth opening; deposition on the joint can cause joint stiffness; deposition in the skull can cause traffic hydrocephalus , mental retardation; deposition in the heart valve, can cause heart valve disease, heart failure; deposition in the internal organs, can cause liver and spleen enlargement, abdominal bulging, inguinal hernia, umbilical hernia, etc.; deposition in the respiratory system leads to tonsils and adenoids Body hypertrophy, narrow airway, thickened vocal cords, often chronic recurrent rhinitis, thick voice, heavy breathing, sleep snoring.
In addition to type II, mucopolysaccharide metabolism disorder is an X-linked recessive genetic disease, and parents are carriers of the disease-causing gene, without any clinical symptoms of mucopolysaccharidosis, but parents also have abnormal genes for the disease. Passed to the child, so the two alleles of the corresponding gene of the disease are abnormal, and the enzyme that degrades the mucopolysaccharide cannot be produced. According to the disease-causing gene and clinical manifestations, the disease is divided into I, II, III, IV. There are 7 types of VI, VII, IX, etc., of which III is divided into four subtypes of IIIA, IIIB, IIIC and IIID, and type IV is divided into IVA and IVB subtypes. Chinese type II is the most common, followed by type IVA. Type IX is rare worldwide and only 2 cases are reported.
Prevention
Mucopolysaccharide metabolic disorder prevention
High-risk families with probands need to do prenatal diagnosis to prevent the same family from being born again. The newborn screening method for the disease is currently under study. It is expected that with the maturity of the technology and the improvement of ethics, the disease will also be diagnosed by prenatal diagnosis by means of neonatal screening, as well as pre-existing symptoms.
Complication
Mucopolysaccharide metabolic disorder complications Complications, deafness, arteriosclerosis
Retinal pigmentation, deafness, chest malformation, hepatosplenomegaly, abdomen, heart valve defects and arteriosclerosis.
Symptom
Mucopolysaccharide metabolic disorders Symptoms Common nostrils Nasal hole or nostril anterior tilting lip Thick tongue Big eyelid edema Joint stiffness Corneal opacity Head malformation Hepatosplenomegaly Eyeball prominent spine kyphosis
(1) Most children with physical developmental disorders show poor growth and short stature after the age of the child; progressive joint distortion, kyphosis or scoliosis, common knee valgus, and claw-like hands. The child's head is large, the face is ugly, the forehead and double eyes are prominent, the hair is many and the hair is low, the eye is cracked, the eye distance is wide, the bridge of the nose is flat, the nostrils are large, the lower jaw is small, and the lips are thick. IS type skeletal lesions are extremely light and usually do not affect height. Type IV lesions are the most serious: the children with vertebral dysplasia are flat, showing short neck, chicken chest, rib rim margin and extreme posterior and scoliosis of the spine; knee valgus is severe; due to the development of the second cervical vertebrae Jiahe joint ligaments are loose and often occur in the atlas subluxation.
(2) The mental and neurodevelopment of children with intellectual disabilities gradually slows down after the age of one, but most of the children with S, IV and VI are intelligent and normal.
(C) Most of the children with eye lesions have corneal opacity around the age of the year, and the type II and IV occur later and lighter. The viscous polysaccharides in the corneal stroma are mainly KS and DS, and the type III enzyme deficiency only causes: HS degradation disorder, so there is no corneal lesion. Types IS, II and III may have changes in retinal pigmentation. IS type can occur with glaucoma.
(4) Others due to the accumulation of mucopolysaccharides in various organs, common hepatosplenomegaly, deafness, heart valve damage, arteriosclerosis, etc. As the disease progresses, secondary lesions such as pulmonary insufficiency, cervical nerve compression symptoms, and traffic hydrocephalus may occur.
Examine
Examination of metabolic disorders of mucopolysaccharide
1. Urine mucopolysaccharide quantification and electrophoresis specimens are best used in morning urine. It can be found that the amount of mucopolysaccharide is increased. Each type has different types of mucopolysaccharides, such as type I and type II, which find dermatan sulfate and heparan sulfate strips. Type III patients found a sulfate heparin band, and type IV patients found a sulfated keratin band. Urine mucopolysaccharide electrophoresis in patients with type III and IV is prone to false negatives.
2. X-ray film The chest radiograph can be found in the ribs like a "banding-like"; the lateral spine shows vertebral vertebral dysplasia, with a "bird-like" protrusion; the left-hand anterior slice shows the proximal metacarpal tip, each The phalanx is like a "bullet".
3. Head CT or MRI can find ventricular enlargement caused by hypertensive traffic hydrocephalus.
4. Determination of peripheral blood lysosomal enzyme activity The selected specimens are peripheral blood leukocytes, skin fibroblasts and plasma. The activity of the enzyme was significantly reduced in patients with mucopolysaccharidosis type I.
5. Mutation detection of lysosomal enzyme-related genes With the current technical means, most patients should detect mutations.
Diagnosis
Diagnosis and differentiation of mucopolysaccharide metabolic disorders
diagnosis
The clinical manifestations of this disease are similar. Therefore, in addition to clinical features, the following tests should be performed:
(1) Skeletal x-ray examination The bone is generally loose and has special morphological changes: the skull is enlarged, the sphenoid is shallow and long; the posterior and scoliosis of the spine is wedge-shaped, and the anterior lower edge of the thoracic and lumbar vertebral bodies is in front of the fish lip. The ribs have small spine ends and widened sternum ends, which are in the form of ribbons; the ulnar and humerus are short and thick, the base of the metacarpal bone is sharpened, and the distal end of the phalanx is narrow.
(2) Urine mucopolysaccharide test is usually carried out by using the toluidine blue coloring method as a screening test for the disease; or the cellulose acetate membrane electrophoresis can be used to distinguish the type of mucopolysaccharide discharged from the urine, and the sputum assists the typing; or the acidity The albumin turbidity method, or the cetyl ammonium chloride pyridine test, was used as a screening. Since HS may be a tablet with a smaller molecular weight.
Differential diagnosis
1. Rickets of vitamin D deficiency is caused by insufficient vitamin D in infants, children, and adolescents, causing disorder of calcium and phosphorus metabolism, resulting in a systemic, chronic, characterized by bone lesions. Nutritional diseases. The main feature is the growth of the long bone metaphyseal cartilage plate and bone tissue calcification, vitamin D deficiency makes mature bone calcification insufficiency.
Second, hypothyroidism (hypothyroidism) is a deficiency or deficiency of thyroxine secretion, the cause of hypothyroidism includes: 1 thyroid parenchymal lesions, such as thyroiditis, surgery or radioisotope treatment caused by excessive destruction of glandular tissue , dysplasia, etc.; 2 thyroxine synthesis disorders, such as long-term iodine deficiency, long-term antithyroid drug therapy, congenital thyroxine synthesis disorder, may be due to an autoantibody (TSH receptor blocking antibody) caused by idiopathic thyroid function Inferior; 3 pituitary or hypothalamic lesions.
