mucopolysaccharide deposition disease
Introduction
Introduction to mucopolysaccharidosis Mucopolysaccharide deposition causes proteoglycan catabolism caused by congenital defects of proteoglycan degrading enzymes will lead to the production of various types of mucopo-lysaccharidoses. It is characterized by excessive accumulation and excretion of oligosaccharides. The metabolic basis of each type of mucopolysaccharidosis is similar but the genetic type and clinical manifestations are different. basic knowledge Sickness ratio: 0.0001% Susceptible people: no specific population Mode of infection: non-infectious Complications: deafness, arteriosclerosis
Cause
Causes of mucopolysaccharidosis
Mucopolysaccharidosis is caused by a congenital defect of the cell lysosomal acid hydrolase, which is characterized by excessive accumulation and excretion of oligosaccharides.
Prevention
Mucopolysaccharide deposition prevention
Mucopolysaccharidosis is caused by congenital defects of lysosomal acid hydrolase. In addition to complying with the Marriage Law, avoiding marriage of close relatives and reducing the incidence of genetic diseases in offspring, there is no effective preventive measure.
According to the statistics of the literature, there are dozens of successful cases of bone marrow transplantation in foreign countries. If the operation is successful, the risk of organ failure can be successfully relieved. Although the child's mental development, bone growth may be slightly worse than normal peers, but There is no problem with the life of a normal person.
Complication
Complications of mucopolysaccharidosis Complications, deafness, arteriosclerosis
Retinal pigmentation, deafness, chest malformation, hepatosplenomegaly, abdomen, heart valve defects and arteriosclerosis.
Symptom
Symptoms of mucopolysaccharidosis disease Common symptoms Humpback liver splenomegaly large neck short corneal opacity convulsion
1. Mucopolysaccharidosis type I (mucopolysaccharidosis)
Also known as Hurler syndrome, lightning damage, AR, is a lack of lysosomal aL-iduronidase, the incidence of 1 / 100,000 newborns, main signs; progressive growth retardation, short stature, mental retardation, boat Head, short neck, rough face, corneal opacity, joint stiffness, limited mobility, hunchback, other: retinal pigmentation, deafness, chest malformation, hepatosplenomegaly, abdomen, heart valve defect and arteriosclerosis, etc. Mucopolysaccharide screening is positive, carriers can be detected according to enzyme activity, and the prognosis is poor, more than childhood death.
2, mucopolysaccharidosis type II (mucopolysaccharidosis)
Also known as Hunter syndrome, XR, no female patients, the incidence rate is 6 / 100,000, is the lack of iduronate sulfatase, the main signs: similar to type I, but no corneal opacity, back is not camel, other: Hairy, progressive deafness; muscle spasm, behavioral paralysis, 2/3 patients after 10 years of age have seizures, biochemical diagnosis such as type I, mainly based on clinical manifestations, heavy ones mostly died before puberty.
Examine
Examination of mucopolysaccharidosis
Mucopolysaccharidosis is caused by congenital defects of cell lysosomal acid hydrolase. According to the etiology, the disease can be divided into eight types. In China, 200 cases have been reported, mainly characterized by severe skeletal malformation and swelling of the spleen. , mental retardation and other malformations, prenatal diagnosis of mucopolysaccharide deposition disease to determine the specific enzyme activity in cultured amniotic fluid cells is the most reliable, but the experimental requirements are high, the general laboratory is difficult to carry out, two simple and practical methods are toluidine blue Semi-quantitative determination by qualitative and uronic acid methods.
1. Toluidine blue qualitative: the method is the same as urine mucopolysaccharide test, the amniotic fluid can be positive in the early pregnancy, and negative in the middle and late pregnancy, such as positive, suggesting that the fetus suffers from mucopolysaccharidosis.
2. Semi-quantitative determination of uronic acid: The acid mucopolysaccharide in amniotic fluid reacts with sodium tetraborate sulfuric acid solution to form uronic acid, which reflects the amount of acid glycopolysaccharide per creatinine. As the pregnancy progresses, the alditol The acid content is gradually reduced, and the reference value of 16-20 weeks of pregnancy is 3.3-7.0 mg/mgCr. If it is higher than this value, mucopolysaccharide depositional fertilizer should be considered. This method has other types of mucopolysaccharidosis other than Morguio syndrome. All have diagnostic significance.
3. Autosomal recessive disorder : The causative gene is on the autosome, and the genetic trait is recessive, that is, only the homozygous is used to show the condition. Both parents of the genetic disease are carriers of the causative gene. Therefore, it is more common in children of close relatives, children have a 1/4 probability of being sick, children have equal probability of disease, and many diseases with abnormal genetic metabolism are autosomal recessive diseases, according to "one gene, one enzyme" ( One gene one enzyme) or the concept of "one cistron one polypeptide", an abnormality of an enzyme or protein molecule of these inherited metabolic diseases, from the abnormality of the respective coding gene, common autosomal recessive inheritance There are lysosomal storage diseases, such as glycogen storage disease, lipid storage disease, mucopolysaccharide storage disease; defects in synthetase such as blood gamma globulin deficiency, albinism; phenylketonuria, liver disease Nuclear degeneration (Wilson's disease) and galactosemia.
Diagnosis
Diagnosis and differentiation of mucopolysaccharidosis
diagnosis
Name code enzyme deficient enzymology determination of sample biochemical changes genetic characteristics Hurler, Scheie syndrome MPSI -L-iduronic acid fibroblasts, white blood cells, tissues, amniotic fluid cells and tissues, DS, HS increased, fibroblasts DS increases autosomal recessive Hunter syndrome MPSII iduronic acid thioesterase serum, fibroblasts, leukocytes, tissues, amniotic fluid, amniotic fluid cells as above X-linked recessive Sanfilippo syndrome A MPSIIIA HS-N-sulfatase (thioamidoase) fibroblasts, white blood cells, tissues, amniotic fluid cells HS increased in urine and tissues, DS increased autosomal recessive Sanfilippo syndrome B MPSIIIB -N acetylglucosaminide serum in fibroblasts Fibroblasts, leukocytes, tissues, amniotic fluid cells appear in the urine as above Sanfilippo syndrome C MPSIIIC Acetyltransferase fibroblasts HS appear in the urine as above Morquio syndrome MPSIV N-acetylgalactosamine-6-sulfatase Fibroblasts KS and CS appear in the urine as above. Morquio syndrome -galactosidase fibroblasts KS appear in the urine. Maroteaux-Lamy syndrome MPSVI N-acetyl galactose Amine 4-sulfatase (aromatic sulfatase B) fibroblasts, white blood cells, tissues, amniotic fluid cells DS appear in the urine as above. -glucuronidase deficiency, nameless disease, MPSVII -glucuronidase Serum, fibroblasts, leukocytes, amniotic fluid cells DS, HS (±) appear in the urine, the same as the unknown disease MPSVIII N-acetylglucosamine 6-sulfatase fibroblasts KS and HS (±) appear in the urine as above
Note: MPS-mucopolysaccharidosis DS-phosphocutaneous dermatan
HS-heparan sulfate CD-chondroitin sulfate
KS- keratan sulfate
Hereditary mucopolysaccharidosis accounts for approximately one-hundred thousand of the babies born.
Differential diagnosis
To identify small and small, rickets and other diseases.
The symptoms of dysplasia are obviously blocked by growth and development, especially the skeletal system and nervous system, such as: (1) short body, long upper body, short lower body, and often accompanied by bone deformities of the extremities, etc., because of thyroid hormone and main length Hormones are essential for long bone growth and normal bone development. (2) Apathy, mental retardation, slow movement, mental retardation, and often deafness, mainly due to the formation of dendrites and axons in nerve cells. The growth of sheath and glial cells, the occurrence and development of nervous system function, and the supply of blood to the brain depend on the proper amount of thyroid hormone. The lack of thyroid hormone causes obstacles in this series of processes. (3) The body temperature is low, the hair is scarce, the facial edema and other common symptoms of hypothyroidism, the height of the child with small babies at birth, body weight, etc. can be no abnormality, until 3 to 6 months, there are obvious symptoms, if After 3 months of birth, the diagnosis is clear, and the addition of thyroxine can make the child develop normally. Once it is found too late, it will delay the early treatment. Effect.
Diagnosis of rickets:
(1) General symptoms: early onset of sleep disturbance, night terror, crying, irritability, after the progress of the disease can be seen muscle relaxation, liver and spleen, abdominal abdomen, sweating, anemia, stunting and so on.
(2) Head: softening of the skull, more common in children less than 6 months, with a finger press at the center of the parietal or occipital bone, there is a table tennis-like elastic feeling, square skull, front sacral extra large, closed delay (can be extended to 2 years old or older) , teething late, no deciduous teeth for more than 10 months, and the dentin is not strong.
(3) Chest: The joint between the rib and the costal cartilage is enlarged, which is called ribbed bead. The sternum is protruding, and the anterior and posterior diameter of the thoracic cavity is enlarged. It is called chicken chest, and the thoracic cavity is recessed along the diaphragm. ditch.
(4) Spine: Multi-directional kyphosis, occasionally side bend.
(5) limbs: the wrist ruler, the humerus bulge, blunt round bulge, called rickety bracelet, lower limbs bent, forming X-shaped legs, O-legs, saber legs and so on.
