Pediatric mucopolysaccharidosis type Ⅳ
Introduction
Introduction to type IV of mucopolysaccharide storage disease in children Mucopolysaccharidosis (MPS), also known as Brailsford syndrome, Brailsford-Morquio syndrome, keratosis sulfate, dysplastic chondrodysplasia, malformed cartilage-bone dystrophy, etc., is a group of congenital genetic diseases, due to adhesion The lack of polysaccharide degrading enzymes can not completely degrade the acid mucopolysaccharide, resulting in the accumulation of mucopolysaccharides in different tissues of the body, resulting in a series of clinical symptoms and signs such as skeletal deformities and mental disorders. basic knowledge Sickness ratio: 0.0001% Susceptible people: children Mode of infection: non-infectious Complications: paraplegia
Cause
Pediatric mucopolysaccharide storage disease type IV etiology
(1) Causes of the disease
This disease, also known as Morquio syndrome, is an autosomal recessive disorder.
(two) pathogenesis
This symptom is mainly caused by the deficiency of N-acetylgalactosamine 6-SO4 lipase. Recently, it has also been reported to be caused by the deficiency of -galactosidase. The osteoblasts of the patient's epiphysis are defective and the formation of articular cartilage is defective. There are cartilage islands in the trabecular bone of the iliac crest, and the calcification preparation zone is deformed. The mucopolysaccharide excreted in the urine is mainly keratan sulfate. The pathological changes are mainly the irregular growth of cartilage and epiphysis, and the arrangement of chondrocytes in the tarsal plate is disordered. Focal aseptic necrosis, vacuolar changes in chondrocytes, poor coloration.
Mucopolysaccharide storage disease type IV has two subtypes, mucopolysaccharidosis type IV A is N-acetylgalactosamine-6-sulfatase deficiency, mucopolysaccharidosis type IV B is -galactosidase deficiency, resulting in sulfuric acid Degradation of keratin and chondroitin sulfate causes these substances to accumulate in cells and tissues. The phenotypes of the two subtypes are the same. Both subtypes are autosomal recessive disorders, N-acetylgalactosamine-6- The full-length cDNA of sulfatase has been cloned, the gene is located on chromosome 16q24.3, and some mutation sites have been found on this gene. The -galactosidase gene has also been cloned, located on chromosome 3q21.33, and found. Mutation site.
Prevention
Pediatric mucopolysaccharide storage disease type IV prevention
Genetic counseling:
Genetic counseling for family history can help affected adults to have selective fertility.
Premarital examination: including a detailed inquiry about the medical history and treatment of both men and women and their family members, especially the presence or absence of congenital malformations, genetic history and close relatives. Family surveys, blood test chromosomal examinations or genetic diagnosis should be performed to detect carriers;
Prenatal consultation:
Pregnant women: medication during pregnancy should be guided by a doctor. Do a good job prenatal checkup. The patient must have a prenatal diagnosis for the child.
Puncture amniocente in pregnancy to check:
1 Increased mucopolysaccharide can be found in amniotic fluid (but not diagnosed before 16 weeks of gestation);
2 After amniocentesis, the cells can be analyzed for early diagnosis, so that the pregnancy can be terminated early.
Complication
Pediatric mucopolysaccharide storage disease type IV complications Complications
Development of quadriplegia, gnome-like, can cause cardiac complications, late pressure paraplegia and respiratory paralysis.
Symptom
Pediatric mucopolysaccharide storage disease type IV symptoms common symptoms saddle nose short neck spine curved corneal opacity limbs weakness liver splenomegaly spine and limb deformity eye wide knee varus knee valgus or hip varus "duck step" gait
Both men and women can be sick. After normal life, the clinical symptoms are obvious after 1 year of age. The bone changes and growth disorders are most prominent. They are characterized by flat vertebrae, knee valgus, thoracolumbar kyphosis, and short trunk with limbs and chest deformities. The growth is stagnant to 6 years old, gnome-like, short neck, short hands and feet, wide fingers, some joint ligaments are loose, joint movement is beyond the normal range, spinal curvature and rib deformity, chest anteroposterior diameter, with chicken breast and short neck Barrel chest, necking when standing, forward leaning, knee, foot valgus, hip, knee flexion like crawling, difficulty in stretching the spine, abdominal distension, dry metaphysis, limited joint activity, and some joints Due to ligament relaxation, joint movement is beyond the normal range, muscle strength is weak, limbs are weak, walking is duck step, intelligence is normal or mild disorder, and its characteristic face is wide eye distance, saddle nose, mouth wide, tooth gap and enamel Dysplasia, maxillary protrusion, corneal opacity and hepatosplenomegaly can occur. Hearing disorder begins around 10 years old. Hearing disorder is almost all over 30 years old. There are reports of cardiac complications caused by chest deformity. Symptoms of spinal cord disease, the development of quadriplegia, abdominal distension, liver and spleen.
Examine
Pediatric mucopolysaccharide storage disease type IV examination
Most of the mucopolysaccharides excreted in the urine of children are keratan sulfate, and occasionally chondroitin sulfate.
For the atypical cases, the following laboratory tests can be performed:
1. Mucopolysaccharide examination of about half of the cases, peripheral blood or bone marrow leukocyte reed or Giemsa staining, can detect dark purple in the lobular nucleus and lymphocytes, abnormal size, different shapes, often become The plexus is present and sometimes contains vacuoles. This granule was once called Reilly granules and was confirmed by histochemistry to be a mucopolysaccharide.
2. Skin fibroblast culture also has the same abnormal staining granules.
3. Urine mucopolysaccharide test The sick children and some relatives have more mucopolysaccharide in the urine.
This type of X-ray shows vertebral dysplasia, the general vertebral body becomes flat, the transverse diameter increases, especially the anteroposterior diameter increases, the anterior edge of the vertebral body is wedge-shaped, the middle part of the anterior border of the vertebral body is like a bird's beak, and the vertebral body is up and down. The margin is irregular, the intervertebral space is widened, and the individual vertebral bodies are small and irregular, and are displaced backwards, causing the posterior vertebral deformity of the spine. It is more common at the junction of the thoracic and lumbar vertebrae. These typical changes occur in the lower thoracic vertebrae and the upper lumbar vertebrae. The second cervical vertebrae odontoid is small or absent, the skull has no obvious changes, the sella is mostly normal, some patients have small or enlarged sella, the distal end of the radius and ulna, the proximal metacarpal has a cone-shaped deformation, and the hip is valgus. The acetabulum is enlarged.
Diagnosis
Diagnostic identification of type IV mucopolysaccharide storage disease in children
1. According to the clinical features of special face and signs, X-ray film performance and laboratory tests, can make a diagnosis.
2. Family history The family history of patients with mucopolysaccharides is helpful for early diagnosis.
Identification with mucopolysaccharide type I, X-ray changes and I type are roughly the same, the difference between the two is this type of spinal bone dysplasia, the vertebral body is generally flat, the leading edge is wedge-shaped, the upper and lower edges of the vertebral body are irregular, the gap is widened, individual The vertebral body develops small and backward displacement, causing posterior vertebral or angular deformity to occur at the junction of thoracic and lumbar vertebrae.
