Enfermedad antimembrana basal glomerular en un paciente transplantado renal con enfermedad de Alport. Research output: Contribution to journal › Article. Pero el conocimiento molecular de estas enfermedades ha hecho que podamos agruparlas bajo otros epígrafes, como son: síndrome de Alport ligado al sexo. The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care.

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CC HPO: Alport syndrome is an inherited disorder of the basement membrane, resulting in progressive renal failure due to glomerulonephropathy, variable sensorineural hearing loss, and variable ocular anomalies review by Kashtan, Alport syndrome is a genetically heterogeneous disorder, with all forms resulting from mutations in genes encoding type IV collagen, which is a major structural component of the basement membrane.

See also benign familial hematuria BFH;a phenotypically similar, but milder disorder. Alport syndrome is also a feature of 2 contiguous gene deletion syndromes involving enfermeead COL4A5 gene: Alport syndrome and diffuse leiomyomatosis and Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis AMME; Alport reported a family in which affected individuals showed progressive renal disease with hematuria and deafness. Affected males died early of uremia, while females lived to old age.

The report of Alport was the fourth concerning a single pedigree that was also studied by GuthrieKendall and Hertz,and Hurst review by Cohen et al. The renal disease became evident as recurrent microscopic or gross hematuria as early as childhood, earlier in males than in females.

Progression to renal failure was gradual and usually occurred ennfermedad males by the fifth decade. The renal histology was nonspecific; both glomerular and interstitial abnormalities, including foam cells, were observed. Although initially reported as a dominant trait with possible partial sex-linkage, it later became apparent that this was an X-linked dominant condition Cohen et al.

The kindred was further studied by O’Neill et al. Men were more severely affected than women. Microscopic hematuria was found to be the most reliable urinary criterion of hereditary nephritis in both males and females.

The hematuria was often accompanied by red cell casts, indicating that the renal lesion was a glomerulitis. There were striking urinary abnormalities in early childhood which progressed to renal failure in adulthood.

Affected women had less obvious urinary findings and rarely developed uremia. Iversen described the characteristic course of Alport syndrome in males: These urinary signs may in one and the same patient vary in degree during the following months, and in some patients they may almost disappear, but they may become more pronounced again during the next infectious disease or after physical strain.

There may be more or less pronounced hypertension Most boys with this disease die from uraemia during adolescence. He had no hearing loss or ocular lesions.

Orphanet: S ndrome de Alport ligado al X

Electron microscopy demonstrated splitting of the lamina densa of the glomerular basement membrane GBM. The proband’s mother had had persistent microscopic hematuria since the age of 40 years but no other manifestations. Transplantation with the kidney of an re donor was followed by rapidly progressive antiglomerular basement membrane nephritis, leading to enfermedda of the transplant almost 7 months after grafting. His affected maternal grandfather died from renal failure at the age of 26 years.

His mother and sister both displayed hematuria. The diagnosis of Alport syndrome was confirmed by the finding of typical glomerular basement membrane abnormalities on a renal biopsy taken at that age. There was progressive renal failure, and she began chronic hemodialysis at age A cadaveric kidney transplantation was done 2 years later. Family history showed that her father had sensorineural hearing loss and endermedad at age 36 of renal failure. An elder sister dnfermedad microscopic hematuria, proteinuria with normal kidney function, and hearing loss.


Molecular genetic studies identified 2 mutations in cis in the COL4A5 gene Microhematuria was first discovered at age 22 years. He reached end-stage renal disease at age 40, and had a successful transplant at age He also had bilateral sensorineural hearing loss and subcapsular posterior lens opacities.

The proband had 2 daughters, aged 15 and 13 years. Since age 2, the older daughter had had mild irregular microhematuria with normal renal function; a renal biopsy at age 8 showed a thinning of the glomerular basement membrane. In the other daughter, microhematuria was discovered at age 7. Ocular and auditory assessments were normal in dde sisters.

The proband’s mother was known to have microhematuria. No father-son affected pairs occurred in any of the kindreds, and enfermedwd was no evidence for autosomal inheritance. One of 3 clinical phenotypes occurred in each of the 23 kindreds: There was some evidence for intrakindred phenotypic heterogeneity for onset of ESRD: Although alporr was clinical variability in ophthalmic signs and the age of development of end-stage renal disease, homogeneity tests failed to show evidence of genetic heterogeneity.

All were consistent with X-linked inheritance, which was xe by linkage studies. Ocular abnormalities have been observed in some patients Arnott et al. Nielsen suggested that anterior lenticonus may be a specific sign of Alport syndrome, since all recently reported cases e.

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Govan described anterior lenticonus and retinal flecks in the macular and midperipheral retina as characteristic ophthalmic findings in Alport syndrome. The findings provided further evidence that Alport syndrome is a hereditary disorder of basement membranes. These abnormalities correlate well with a defect in the type IV collagen molecule. Their patient was a year-old man who had recurrent episodes of aplort in 1 or both eyes, which awakened him at night, and were associated with lacrimation, photophobia, and blurred vision.

Proteinuria and microscopic hematuria had been recognized by age 12 months, and bilateral sensorineural hearing loss since age 11 years. Colville and Savige reviewed the ocular enfermedac of Alport syndrome. The ocular manifestations were identical to those found in the autosomal forms of Alport syndrome. In 2 of them, 2 episodes over a period of 1 to 3 years had occurred; the third brother had approximately 60 episodes over the previous 10 years.

Similar studies of the anterior lens capsule of a patient with Alport syndrome who had anterior lenticonus showed lack of immunoreactivity to the COL4A3 to COL4A6 chains.

Hasstedt and Atkin restudied the Utah kindred, ‘family P,’ that was the subject of the studies of Perkoff et al. Penetrance was estimated as 0.

Reexamination of segregation showed no excess of affected offspring of affected parents and no difference in penetrance in daughters of symptomatic and asymptomatic mothers. An unexplained deficiency of sons of affected mothers was aloort. In affected Utah kindreds, Menlove et al. They found 2 of 21 recombinants with DXS3, which is located at Xq They found a maximum lod score of 2.

These authors referred to the disorder as ‘Alport ee hereditary nephritis,’ based on the assumption that the disorder fe described by Alport was autosomal dominant. Lod scores in excess of 3. Two types of Alport syndrome were represented by 3 kindreds: However, there was no evidence of linkage heterogeneity among these families.



Flinter and Bobrow studied 41 families and concluded that Alport syndrome may be less heterogeneous than previously thought. All of the families had ‘classic’ Alport syndrome, with pedigrees compatible with X-linked inheritance.

They confirmed linkage to Xq markers. Four deletions and 1 single base mutation of the COL4A5 gene were detected. Myers and Tyler found variability in the histologic findings of the ear in Alport syndrome.

In 2 cases with severe deafness, 1 had had a histologically normal inner ear, whereas the other had a marked reduction in spinal ganglion cochlear neurons. Spear suggested that a primary structural abnormality of basement membranes underlies the phenotype of Alport syndrome. Churg and Sherman stated that the ultrastructural changes of the glomerular basement membrane, which is irregularly thickened and attenuated, are specific for Alport syndrome. Immunofluorescence studies provided little evidence for an immunologic basis for renal damage.

In a study by WaldherrAlport syndrome comprised at least a sixth of familial glomerular disease, which itself was responsible for 6. The most common abnormality on electron microscopy, found in 27 of 31 biopsies, was complex replication of the lamina densa of the capillary basement membrane to form a ‘basket weave’ pattern. These changes could be seen in children under age 5 years.

If neurosensory deafness or heavy proteinuria was present, the patient generally ran a progressive clinical course and fell within the spectrum of Alport syndrome.

In contrast, patients from families without deafness, heavy proteinuria, or chronic renal failure showed a nonprogressive course consistent with benign familial hematuria Their biopsies showed little or no glomerular changes other than attenuation of the lamina densa on electron microscopy.

By indirect immunofluorescence of kidney biopsies from 7 males from 5 families with Alport syndrome, Jeraj et al. However, the antigen was detected in 2 affected women, an unaffected male, and 13 normal controls. The specificity of the finding was supported by persistence of other glomerular basement membrane antigens, and the findings were compatible with X-linked inheritance.

The epitopes reactive with anti-GBM antibodies are located in the noncollagenous globular domain of type IV collagen. Treatment with acid-urea favors exposure of this epitope. The immunofluorescent stains of basement membrane demonstrated the Lyon phenomenon of X inactivation in a particularly graphic manner. These studies indicated that the FNS antigen is apparently distinct from the Goodpasture antigen.

In a retrospective, double-blind study, Savage et al. Strong linear binding of MCA-P1 to GBM was found in all 29 patients without evidence of hereditary nephritis and in 2 with possible but not definite hereditary nephritis.

In contrast, 12 of 13 patients with strong evidence of hereditary nephritis showed no binding 9 or greatly reduced binding 3. Thus, abnormal antigenicity of the basement membrane in hereditary nephritis, as reported by McCoy et al. In 30 cases, aalport was hematuria in at least 1 other member of the family; in the other 18 cases, there was no familial incidence.

There were no differences between the 2 groups with regard to clinical and pathologic findings. At the latest follow-up, 6 boys with familial hematuria and 3 boys with nonfamilial hematuria had reduced renal function, and 9 boys with familial hematuria and 4 boys and 1 enfermedsd with nonfamilial hematuria had sensorineural deafness.