Pediatric Homocystinuria
Introduction
Introduction to Pediatric Homocytosis Homocystinuria is a hereditary disease caused by enzyme deficiency during methionine metabolism. The main clinical manifestations are multiple thromboembolism, mental retardation, crystal ectopic and excessive finger toe. basic knowledge The proportion of illness: 0.0008% Susceptible people: children Mode of infection: non-infectious Complications: crystal dislocation, thrombosis, glaucoma
Cause
Pediatric isoform cystineuria etiology
(1) Causes of the disease
The disease is an autosomal recessive genetic disease, the gene is located on the long arm of chromosome 21, and the disease has at least 3 different biochemical defects:
Methyltransferase deficiency (26%):
Methyltetrahydrofolate-homocysteine methyltransferase-deficient type ("Methyltransferase type") is a disorder in which the homocysteine is converted to methionine by methyltransferase, vitamin B12 It is a coenzyme of methyltransferase.
Reductase deficiency (25%):
3.5, 10-N-Methyltetrahydrofolate reductase deficiency type ("reductase type") Normally, the reductase provides a methyl group for homocysteine to be converted into methionine. When the enzyme is deficient, the isotype When the methylation of cysteine is insufficient, it accumulates in the body together with homocysteine.
Synthetic enzyme deficiency (30%):
The cystathionine synthase-deficient type ("synthetase type") is a metabolic pathway from homocysteine to cystathionine, which is the most common type.
(two) pathogenesis
Synthetic enzyme-type lesions are mainly found in various blood vessels. In the blood vessels of various organs, including brain tissue, there is thickening and fibrosis. There may be thrombosis, the aorta may be narrowed or dilated, and there are multiple infarcts in the brain. The disease often has crystal ectopic and skeletal malformations. These pathological changes may be caused by excessive homocysteine-activated coagulation factors, inhibition of collagen formation, and abnormal connective tissue. Vitamin B6 is a coenzyme of cystathionine synthase. Therefore, the application of large doses of B6 is effective in some cases.
Prevention
Pediatric homocysteine prevention
The determination of various genetic defects depends on the enzymatic analysis of culture cells. The diagnosis of this disease depends on the enzyme activity. The activity of the enzyme can be measured by skin fibroblasts. Heterozygotes can also be detected by this method. The prenatal diagnosis can be used to measure amniocytes. Enzyme activity, antenatal diagnosis of hereditary metabolic disease is one of the effective measures to prevent the occurrence of genetic diseases. It is the practical application of human genetics knowledge and an important measure for eugenics.
Amniocentesis can be performed through the abdominal wall 17 to 20 weeks of pregnancy. The amniotic fluid cells are epithelial cells that are shed by the fetus. After culture, enzyme activity or genetic analysis can be performed. The fetal loss rate caused by this method is 0.5%. It is still an important means of prenatal diagnosis.
The villi are from the embryonic trophoblast. They can be taken from the abdominal wall by 10 to 12 weeks of gestation. They can be used for enzyme activity determination or genetic analysis. The advantage is that the amniocentesis is 2 months earlier than the amniocentesis. It is not necessary to culture, and the prenatal diagnosis can be obtained earlier. As a result, once the fetus is sick, the pregnant woman can choose artificial abortion in time, the subsequent operation is relatively easy, and the psychological burden of the pregnant woman can be relieved as soon as possible.
Prerequisites for prenatal diagnosis are accurate diagnosis of the proband. It is only possible for the mother to check for an enzyme or a genetic test in the prenatal diagnosis when she is pregnant again, especially the prenatal genetic diagnosis, except for the missing and The PCR/ASO method can directly detect gene defects, and other linkage analysis methods are based on clinical diagnosis. The reason is that some genetic diseases have genetic heterogeneity, and the same disease phenotype can be caused by mutations of multiple loci, for example. Muscular dystrophy, more common is DMD/BMD, but there are other genetic mutations that can cause muscular dystrophy. If the clinical diagnosis is inaccurate, the genetic diagnosis of B disease with the polymorphic site of A disease is bound to be introduced. Misleading, leading to diagnostic errors, and secondly to avoid sample contamination, the contamination of maternal DNA in fetal materials can not be ignored, bloody amniotic fluid is often one of the root causes of diagnostic errors, severe bloody amniotic fluid must be removed by culture to remove pregnant women's white blood cells, villi After collection, it is necessary to check and select under the inverted microscope to remove the endometrial tissue.
Due to the serious condition of lysosomal storage disease, most diseases have no effective treatment and the prognosis is poor. The birth of the child brings a heavy economic and mental burden to the society and the family. There is no effective treatment for this disease, but most of them can be It is clear before birth that the fetus is sick, and some can also make prenatal diagnosis in the early pregnancy. It has the meaning of "prevention" in eugenics, because it can prevent the birth of the fetus based on the clear prenatal diagnosis. It is the only viable eugenics measure that can reduce the burden on families and society and improve the quality of the population.
Complication
Pediatric homocystinuria complications Complications, dislocation, thrombosis, glaucoma
Visible bone abnormalities, crystal dislocation, thrombosis, mental retardation, convulsions, etc., often accompanied by glaucoma, retinal detachment, thrombosis of various parts of the blood vessels, multiple cerebrovascular accidents can cause hemiplegia, pseudobulbar palsy.
Symptom
Pediatric homocysteine symptoms common symptoms urine has a special rat odor osteoporosis hair thin skin pattern spider refers to mental retardation microthrombus formation convulsion
1. Synthetic enzyme deficiency type: Typical symptoms are seen in cases of cystathionine synthase deficiency type. The child is normal at birth and 5 to 9 months. The main symptoms are skeletal abnormalities, crystal dislocation, thrombosis, and mental development. Backward, horrified, etc., skeletal deformities have limbs and fingers toe slender (spider finger toe), easily mistaken for Ma Fang syndrome, X-ray examination showed osteoporosis, vertebral body back bi-concave, and scoliosis Etc., there are many dislocations of the eye symptoms, mostly in the 3 to 10 years old, often accompanied by glaucoma, retinal detachment, thrombosis can occur in any organ, about 50% of cases have had one or more thromboembolic episodes, cranial Internal blood vessels, coronary arteries, renal arteries, pulmonary blood vessels, skin blood vessels, etc. may have thrombosis, and the corresponding symptoms appear, the nervous system symptoms are more obvious, may have mental retardation, seizures, multiple cerebrovascular accidents may cause hemiplegia, Pseudobulbaric palsy, may also have psychiatric symptoms, other symptoms can also be seen, such as crotch flushing, skin marble pattern, thin skin, hair thin and easy to fold, prothrombin reduction, myopathy.
2. Methyltransferase deficiency type: The "methyltransferase deficiency type" of this disease is mild, and may have skeletal deformities, physical and mental retardation, but rare crystal ectopic and thrombosis, this type can also Combined with methylmalonic aciduria.
3. Reductase deficiency type: The "reductase deficiency type" of this disease is mainly caused by nervous system symptoms such as convulsions, mental retardation, schizophrenia-like symptoms, myopathy, etc., no bone deformity, crystal ectopic, no vascular symptoms .
Examine
Pediatric homocysteine examination
1. Determination of urinary homocysteine: Screening method can be used, ie sodium nitroprusside test: 1ml of urine is added to 5% aqueous solution of sodium cyanide, placed for 5 minutes, 1 drop of 5% sodium nitroprusside solution is added, red or magenta appears. Positive, indicating an excess of sulfur-containing amino acids in the urine.
2. Diagnosis depends on enzyme activity: The activity of the enzyme can be measured by skin fibroblasts, and heterozygotes can also be detected by this method.
3. Prenatal diagnosis: The enzyme activity of amniotic fluid cells can be measured. X-ray, B-ultrasound, CT and other imaging examinations should be done.
Diagnosis
Diagnosis and diagnosis of homocystinuria in children
Confirmed according to clinical manifestations and laboratory tests.
The disease needs to be differentiated from the horse square syndrome. The commonalities of the two are crystal ectopic, spider finger toe, cardiovascular symptoms, but the genetic pattern and disease development are different. The disease is recessive, and the horse syndrome is autosomal. Dominant inheritance, the toe slender can be seen from birth; while homocystinuria is normal in primary life, bone growth is not proportional after several years, and limbs are lengthened, in addition to thromboembolic symptoms, osteoporosis, Vertebral bone has a biconcave deformity, etc., more importantly, Ma Fang syndrome does not have the biochemical metabolic abnormalities of this disease.
