hereditary nephritis
Introduction
Introduction to hereditary nephritis Hereditary nephritis (Alport syndrome, AS) is a hereditary glomerular basement membrane disease mainly characterized by hematuria, progressive renal function loss, sensorineural deafness and ocular abnormalities. A disease caused by a mutation in the main collagen component of the basement membrane-IV collagen gene. The incidence of genetic mutations is about 1/10000~1/5000. According to hereditary methods, it can be divided into 1X chain dominant inheritance (X-linkeddominant, XL, about 80%). The disease-causing gene is on the X chromosome, and heredity is related to gender. 2 autosomal recessive (AR; about 15%), the causative gene on the autosome. 3 autosomal dominant, AD; very few. They were caused by mutations in the genes COL4A5 and/or COL4A6, COL4A3 and/or COL4A4, which encode different chains of type IV collagen, respectively. basic knowledge Sickness ratio: 0.0001% Susceptible people: no special people Mode of infection: non-infectious Complications: Psychosis Autoimmune thyroid disease-associated nephropathy Selective IgA deficiency Posterior optic neuritis Ascending aortic aneurysm Congenital anorectal malformation
Cause
Cause of hereditary nephritis
The 6-type collagen of the type IV collagen is polymerized into three triple-strand molecular structures called monomers, and the monomers are polymerized to form dimers or tetramers, which are then twisted together to form a collagen network structure. The gene mutation of X-linked dominant inheritance Alport syndrome mainly occurs in the gene encoding type IV collagen 5 chain (COL4A5). Gene mutations in autosomal recessive Alport syndrome occur on the chromosome 2 gene encoding the type IV collagen 3 chain or 4 chain (COL4A3/COL4A4).
Prevention
Hereditary nephritis prevention
Care should be taken to avoid infection, fatigue and pregnancy, and nephrotoxic drugs should also be banned to prevent the disease from occurring.
Complication
Hereditary nephritis complications Complications psychosis autoimmune thyroid disease-associated nephropathy selective IgA deficiency posterior optic neuritis ascending aortic aneurysm congenital anorectal malformation
In the family of hereditary nephritis, patients often have many non-specific lesions, such as thyroid disease, IgA deficiency, retrobulbar optic neuritis, ascending aortic aneurysm, anorectal malformation, psychosis, and fibromuscular dysplasia.
Symptom
Hereditary symptoms of nephritis Common symptoms Protein hematuria Hearing impaired
Alport syndrome is essentially a hereditary, kidney-based clinical syndrome. Therefore, in clinical practice, it must pay attention to the characteristics of renal abnormalities, but also pay attention to "extra-renal" performance, but also through family history. Try to infer the hereditary type, because the clinical manifestations and prognosis of different types of Alport syndrome are different.
Kidney performance
Hematuria is the most common, mostly glomerular hematuria. Data from China have reported that 68% of patients with Alport syndrome are glomerular hematuria. Male patients with X-linked dominant hereditary manifestations of persistent microscopic hematuria may even have hematuria within a few days after birth; the penetrance of microscopic hematuria is 100%. About 67% of men with Alport syndrome have paroxysmal gross hematuria. Most of them are 10 to 15 years old. Gross hematuria can occur after upper respiratory tract infection or fatigue. Some authors believe that boys in the family of X-linked dominant hereditary Alport syndrome, if no hematuria is found by the age of 10, the boy is likely to be unaffected. More than 90% of female patients with X-linked dominant Alport syndrome have microscopic hematuria, and a few female patients have gross hematuria. Almost all patients with autosomal-negative heredity (both male and female) show hematuria; in heterozygous relatives of autosomal recessive hereditary, the incidence of hematuria is 50-60%, not more than 80%.
In male patients with X-linked dominant Alport syndrome, proteinuria occurs, which is characterized by persistent proteinuria with age or hematuria, and even nephrotic proteinuria. The incidence of nephrotic syndrome is 30-40%. The first hospital of Peking University reported that the level of proteinuria nephrotic syndrome accounted for 31.8%, and suggested a poor prognosis. Similarly, the incidence and severity of hypertension also increases with age and occurs mostly in male patients.
Hearing impairment
Hearing impairment in patients with Alport syndrome is a sensorineural deafness that occurs in the cochlea. The deafness is progressive, the bilateral sides are not completely symmetrical, and the initial hearing loss in the high-frequency area requires diagnosis by the audiometer, gradually becoming full-range, and even affecting daily conversations. At present, there are no reports of congenital deafness. Men with X-linked dominant hereditary Alport syndrome have a higher incidence of deafness than women, and their age is earlier than that of women. The incidence of male and female deafness in X-linked dominant Alport syndrome was reported to be 81% and 19%, respectively. About 66.6% of patients with autosomal recessive Alport syndrome showed sensorineural deafness before the age of 20 years.
Ocular lesion
The characteristic ocular lesions of Alport syndrome include anterior cone lens, point-like and spotted retinopathy around the fundus macular, and retinal eretinopathy. The anterior conical lens appears as a forward sac in the central part of the lens, and the patient may present with progressive myopia and even cause spontaneous perforation of the anterior polar cataract or anterior capsule. The anterior conical lens appears more than 20-30 years old. The smallest patient reported so far is a 13-year-old male, 60-70% X-linked male, 10% X-linked dominant hereditary female, and about 70% of the permanent staining. Patients with recessive hereditary Alport syndrome develop a anterior conical lens. Alport syndrome-specific retinopathy usually does not affect vision. Using ophthalmoscopy or retinal imaging, there are dim, even pale, spotted and spotted lesions around the macula or retina in the retina. The lesions are accompanied by a decline in renal function. progress. About 70% of X-linked dominant hereditary men, 10% of X-linked dominant hereditary women, and about 70% of patients with often-stained recessive hereditary Alport syndrome develop retinopathy and often coexist with deafness and anterior conical lens. However, retinopathy occurs earlier than the pre-conical lens. At present, there have been no reports of patients with autosomal dominant Alport syndrome with ocular involvement.
Abnormal blood system
It is currently believed that AMME syndrome is Alport syndrome with abnormal blood system, mainly manifested by Alport, mental abnormality, mid-facet dysplasia and elliptic polycythemia. Studies have confirmed that all of the Alport syndrome COL4A5 genes are deleted, and the gene deletion range exceeds the 3' end. In addition, previously reported blood system abnormalities, such as giant platelets, platelet abnormalities with leukocyte inclusions, and only platelet abnormalities accompanied by "Alport-like" manifestations, have been confirmed to encode non-myosin heavy chain 9 gene The MYH9 mutation is caused by a mutation in the type IV collagen gene. Therefore, such diseases are not Alport syndrome, called MYH11A syndrome, which is autosomal dominant.
Diffuse leiomyoma
Some adolescent Alport syndrome families or patients have significant smooth muscle hypertrophy, and the esophagus, trachea, and female reproductive tract (such as the clitoris, labia majora, and uterus) are the most common sites of involvement, with symptoms such as dysphagia and breathing. Difficulties, etc.
other
Some authors have reported some diseases such as thyroid disease, IgA deficiency, pons neuritis, ascending aortic aneurysm, anorectal malformation, psychosis, fibromuscular dysplasia, type I neurofibromatosis and Turner-like syndrome. . At present, the above lesions can not be determined as a specific clinical manifestation of Alport syndrome, and it is likely to be a disease in which Alport syndrome coexists.
Examine
Examination of hereditary nephritis
Hematuria and proteinuria, male patients showed persistent microscopic hematuria. At the beginning, it was only microalbuminuria. Urine protein gradually increased with age and often developed into nephrotic syndrome proteinuria. There may be platelet defects and a significant tendency to hemorrhage. When renal failure occurs, there may be changes in urea nitrogen and creatinine.
1. Light microscopy There is no specificity of renal lesions under light microscopy. Early glomerular lesions in the disease are generally normal, only mild focal segmental mesangial tissue hyperplasia, with the progression of the disease, glomerular progression to glomerular sclerosis, advanced glomerular fibrosis and spheroidal sclerosis, The renal interstitial can progress from inflammatory cell infiltration to fibrosis with tubular atrophy.
This disease is common in interstitial foam cells at the junction of kidney and medulla. The foam cell cytoplasm contains neutral fat, mucopolysaccharide, cholesterol and phospholipids. The lesion is not specific to the disease, but the incidence of this disease is high, which is still important for suggesting this syndrome.
In addition, 10% to 25% of patients with Alport syndrome have fetal glomeruli. Fetal glomeruli can also be seen in children with non-Alport syndrome, especially those with congenital nephrotic syndrome, but after 5 years of age, it is difficult to see this lesion in non-Alport syndrome. This fetal glomerulus is mainly seen in children before the age of 10, especially in infants before the age of 5. Adult Alport syndrome patients are rare.
2. Electron microscopy The ultrastructural changes of the glomerular basement membrane (GBM) have diagnostic significance for this disease and are earlier than optical microscopy. There are three main types of lesions: GBM thickening, thinning and the two. The thinned GBM often only reaches 1/4 of the normal thickness, which is more common in children and women; the thickened GBM can reach 2 to 5 times the normal thickness, and the epithelial side edge is often irregularly wavy, thickened and dense. With longitudinal splitting and delamination, they are interlaced into each other. The mesh contains lipid particles, which are more common in adults and men. If the thickened GBM is widespread and appears with the thinned GBM, it makes a lot of sense for the diagnosis of this disease. Pure GBM thinning without GBM thickening is more common in benign familial hematuria, thin basement membrane nephropathy. Some authors have found that the degree of GBM thickening and rupture is parallel with the degree of proteinuria. Patients with markedly thickened GBM and rupture often progress, and the prognosis is poor (especially in male patients).
3. Immunofluorescence Immunofluorescence and immunohistochemistry were mostly negative, suggesting that no humoral immunity is involved in the disease. Occasionally, a small number of glomerular capillaries have IgM and C3 deposits. Immunofluorescence also found that GBM in patients with Alport syndrome lacks Goodpasture antigen and lacks amyloid P. Amyloid P is present in normal human plasma and GBM, and the significance of GBM deficiency of amyloid P in patients with Alport syndrome remains to be studied.
In addition, the authors used anti-GBM antibodies produced by kidney transplantation in patients with Alport syndrome or directly anti-5 (IV) antibodies to incubate the skin slices of patients with this disease treated with acid-urea. As a result, the epidermal basement membrane of male patients with Alport syndrome was completely No coloration, female patients only segmental coloration, similar to the results of GBM staining, this theory theoretically suggests that the GBM and epidermal basement membrane of patients with this disease lacks Goodpasture syndrome antigen, and in practice it is possible to provide a diagnosis of this disease. means.
Diagnosis
Diagnosis and treatment of hereditary nephritis
The current diagnosis of Alport syndrome is mainly based on clinical manifestations, family history, tissue basement membrane IV collagen chain immunofluorescence, renal biopsy and genetic analysis.
1, clinical manifestations of clinical manifestations of hematuria and progressive renal insufficiency, accompanied by ear lesions (high-frequency sensorineural deafness) and ocular lesions (conical cornea, anterior spherical lens, macular fovea, etc.) Extrarenal performance.
2. Family history should have a positive family history. Detailed and objective pedigree maps should be drawn as much as possible, paying particular attention to the urine test results of the family members, renal function, presence of deafness and eye abnormalities.
3, tissue basement membrane IV collagen chain immunofluorescence test using anti-IV collagen different chain monoclonal antibody, immunofluorescence in renal biopsy and simple skin biopsy tissue, can be used to diagnose X-linked hereditary Alport syndrome patients , screening gene carriers and judging heredity.
4, renal biopsy tissue electron microscopy according to electron microscopic glomerular basement membrane typical lesions can be diagnosed. However, the renal tissue lesions of young male patients, female heterozygotes of any age, and individual adult male patients are only diffuse thinning of the glomerular basement membrane or predominantly.
5, genetic analysis is very important for the determination of hereditary type, gene carriers for prenatal diagnosis, but also for clinical and pathological examination results are uncertain case diagnosis.
