nail-bone tetralogy
Introduction
Introduction Defects or hypoplasia of the nail, unilateral or bilateral humeral loss or dysplasia of the posterior tibia, elbow and valgus valgus deformity, etc., known as nail-bone quadruple syndrome. The nail-patella syndrome (nail-patellasyndrome) is aliased as hereditary bone-to-finger dystrophy (hereditaryosteo-onychodysplasia); hereditary skeletal atrophy; nail knee syndrome; hyperthyroidism syndrome; It is a hereditary disease characterized by dysplasia or loss of the tibia, nail dystrophy, elbow dysplasia, sacral horn and renal failure. The clinical feature of this disease is nail-bone quadruple: (1) Nail defect or dysplasia. (2) humeral hypoplasia or absent. (3) posterior sacral spurs. (4) Elbow and hip valgus deformity.
Cause
Cause
The syndrome is autosomal dominant, and the locus is linked to the adenylate cyclase and ABO blood group on chromosome 9.
At present, little is known about the pathogenesis of this syndrome. Some people think that it is a collagen disease, and there are abnormalities in the process of collagen synthesis, assembly or degradation. The cytological mechanisms of this disease have not been studied. The lack of non-glomerular basement membrane damage in pathological changes suggests that the various damages in this syndrome may be due to different mechanisms, and not all lesions are associated with basement membrane abnormalities.
A small number of patients developed anti-glomerular basement membrane nephritis, supporting the hypothesis that glomerular basement membrane components are abnormal. Using a monoclonal antibody against the Goodpasture epitope, it was found that the glomerular basement membrane of 2/3 patients with renal biopsy specimens did not bind to the monoclonal antibody, suggesting a basement membrane for this syndrome. The component's health search to some degree of heterogeneity also suggests the presence of Goodpsture antigen deletion or alteration. It is worth noting that it is not clear whether this is a primary or secondary change in this syndrome. Laboratory examination: There may be different degrees of proteinuria, microscopic hematuria and tubular urine, decreased urine concentration, abnormal uric acid or protein secretion. 30% of kidneys will develop slowly to renal failure, and there may be uremia changes in renal failure.
Examine
an examination
Related inspection
Glomerular filtration fraction serum complement C1q serum C1q glomerular filtration fraction (GFF) anti-glomerular basement membrane antibody assay (AGBM)
Clinical manifestations:
1. Kidney performance: More than half of the nail-sacral syndrome patients have no obvious clinical manifestations of the kidney. In patients with clinical renal manifestations, the characteristic manifestation is benign nephropathy. The most common symptoms are different degrees of proteinuria, microscopic hematuria and tubular edema and hypertension. In a study, 56% of patients had abnormal sediment in the urine. There is damage to urine concentration, abnormal uric acid or protein secretion. 30% of kidneys will develop slowly to kidney failure and die of uremia. Meyrier et al reported that two families showed a diversity of progression of renal lesions. In one family, a 64-year-old male patient has a proteinuria that lasts for 20 years, with only mild insufficiency in his kidney function and his brother died of kidney failure at the age of 25.
One of the twin brothers of another family gradually developed into end-stage renal failure, while the other long-term only proteinuria. The literature shows that the degree of ultrastructural damage appears to have little to do with the severity and duration of clinical manifestations of health searches; the number of kidney stones is not equal to the number of congenital urinary tract malformations.
2. Skeletal and nail damage: The syndrome refers to abnormalities of the nails including discoloration, spoon-shaped nails, longitudinal tendons, finger nails or nutritional disorders, and triangular nail shadows. These performances are often symmetrical, and the health search is in 80% to 90% of patients.
Nail is more susceptible to nails and has the highest frequency of thumb involvement. About 60% of patients have humeral loss or dysplasia. These changes may be related to a reduction in the lateral side of the joint during flexion, which can lead to knee valgus deformity. Abnormal humerus can also cause osteoarthritis osteoarthrosis and joint effusion. 80% of patients with this syndrome have an open humerus, which protrudes forward and upward, called the humeral horn. Elbow abnormalities include dysplasia, posterior process of the distal radius, resulting in increased angle and extension of the lifting angle, limited supination function, and associated humeral head dysplasia and ankle joint abnormality. In the above manifestations, the loss of nails or hypoplasia, unilateral or bilateral humeral loss or dysplasia of the posterior tibia, elbow and valgus valgus deformity, etc., is called nail-bone quadruple syndrome.
3. Others: In addition to glomerular basement membrane defects, radiological examination revealed other structural abnormalities in the kidney and urinary tract of the syndrome, including: pyelectasis and cortical scars, suggesting vesicoureteral reflux; unilateral nephrotic condensation Double ureter and double renal pelvis; unilateral renal dysplasia and contralateral kidney; pelvic blunt and kidney stones.
Other auxiliary inspections:
1. Light microscopy: The performance of glomeruli under light microscopy is quite variable. Patients without renal dysfunction usually have normal or near normal glomeruli. Health Search In some typical cases, partial capillary basement membrane thickening can be seen but not ubiquitous. Global or focal glomerulosclerosis can also be seen, which is related to the level of renal dysfunction, especially the degree of proteinuria. Related, suggesting the role of proteinuria in the progression of renal damage in this syndrome. Others may have epithelial cells and endothelial cells with anti-glomerular basement membrane disease, crescents, tubule atrophy and interstitial fibrosis and renal dysfunction parallel to arterial intimal fibrosis, arterioles, etc. At this time, it is often suggested that there is hypertension
2. Immunofluorescence: Because the syndrome is not immune-mediated, glomerular immunohistochemistry results are often negative. In global or segmental glomerular sclerosis, irregular and focal sedimentary deposits of IgM, C3, C1q, or both may be observed in the capillary wall or glomerular mesentery or Both have a distribution related to the stage and extent of glomerular sclerosis.
When other pathological changes are complicated, immunofluorescence may be positively found in patients with concurrent glomerular basement membrane disease. It can be seen that IgG and C3 are linearly deposited in all glomerular capillaries, and fibrin deposition in capillaries is new. The performance of the moon body formation. The link between this syndrome and anti-glomerular basement membrane disease is unclear. It is possible that healthy search refers to persistent and severe damage to the glomerular basement membrane in patients with nail-to-sacral syndrome. The antigenicity leads to antibody production. Mackay et al reported that a patient with nail-sacral syndrome and membranous glomerulonephritis showed uniform granular IgG deposition on all capillary walls.
3. Ultrastructure: Regardless of the glomerular performance of the patients under the light microscope, and regardless of the clinical or renal symptoms such as proteinuria, the ultrastructure of the glomerular basement membrane is changed. Common and characteristic lesions are ultrastructural abnormalities of the glomerular basement membrane. A large number of patchy translucent substances are seen in the whole layer of the basement membrane. This kind of thing is sometimes seen in the mesangial matrix. "Moth" performance.
Dyeing with standard lead citrate sometimes results in coarse fibrils and cross-banded collagen in the glomerular basement membrane and mesangial matrix. It is more common to dye the above substances with phosphotungstic acid. The fibrils are located in small clusters located in the basal membrane of the glomerulus or along the entire glomerular basement membrane. The thickness of the glomerular basement membrane is not uniform, and the thickness of the glomerular basement wall can vary from normal to thick. In the thickened part of the glomerular basement membrane, the translucent band is more and more prominent. The glomerular mesangial matrix is also increased in some cases with translucent substances and collagen fibers. The non-small basement membrane of the kidney is free of translucent and collagen-like fibrils, and the changes of the basement membrane of the renal tubule are chronic tubulointerstitial nephropathy-like lesions, which are consistent with glomerular damage in the late stage. In most cases, there is no electron dense deposit. The glomerular visceral epithelial cells often decrease or disappear, and the degree of reduction is related to the severity of proteinuria.
Diagnosis
Differential diagnosis
Differential diagnosis of nail-bone quadruple syndrome:
1. Nail dystrophy: refers to nail-patella syndrome or hereditary osteo-dystrophic disease (hereditary osteo-onyx dysplasia), which is a hereditary disease characterized by tibia Dysplasia or loss, nail dystrophy, elbow dysplasia, sacral horn and renal failure.
2, there are missing marks on the tip of the nail: the lack of marks on the tip of the nail refers to the symptom of the lack of marks on the tip of the nail.
