[Alport syndrome. Report of two cases]. / Repercusiones oculares del Síndrome de Alport: A propósito de dos casos.

Alport syndrome is an inherited progressive form of glomerular disease that is often associated with sensorineural hearing loss and ocular abnormalities. We report two men with Alport syndrome. Both had chronic kidney disease and consulted for long-term loss of visual acuity. One had auditory abnormalities. On the ophthalmological examination, both had anterior lenticonus and one had dot or fleck retinopathy. Those findings are described in up to 50% and 70% of men with X-linked Alport syndrome, respectively. Both patients had a family history of Alport syndrome or suggestive signs and symptoms.

Repercusiones oculares del Síndrome de Alport: A propósito de dos casos / Alport syndrome. Report of two cases

Alport syndrome is an inherited progressive form of glomerular disease that is often associated with sensorineural hearing loss and ocular abnormalities. We report two men with Alport syndrome. Both had chronic kidney disease and consulted for long-term loss of visual acuity. One had auditory abnormalities. On the ophthalmological examination, both had anterior lenticonus and one had dot or fleck retinopathy. Those findings are described in up to 50% and 70% of men with X-linked Alport syndrome, respectively. Both patients had a family history of Alport syndrome or suggestive signs and symptoms.

Female Patient with Alport Syndrome and Concomitant Membranous Nephropathy: Susceptibility or Association of Two Diseases?

Alport syndrome (AS) is a disorder of collagen IV, a component of glomerular basement membrane (GBM). The association of AS and immunocomplex nephropathies is uncommon. This is a case of a 37-year-old woman with family history of X-linked AS, including 4 affected sons. This patient developed full-blown nephrotic syndrome along a 3-month period, a presentation not consistent with AS progression. This scenario suggested an alternative diagnosis. A kidney biopsy was therefore performed, showing membranous nephropathy (MN) in addition to GBM structural alterations compatible with AS. Whole exome sequencing also confirmed the diagnosis of X-linked AS, revealing a heterozygous pathogenic mutation in COL4A5. While a negative serum anti-phospholipase A2 receptor did not rule out a primary form of MN, it was also uncertain whether positive serologic tests for syphilis could represent a secondary factor. It is currently unknown whether this unusual association represents AS susceptibility to immunocomplex-mediated diseases or simply an association of 2 disorders.

Evolução da síndrome de alport em crianças brasileiras / The evolution of alport syndrome in Brazilian children

Objetivo: Apresentar a evolução de crianças com Síndrome de Alport e determinar manifestações preditivas de Insuficiência renal crônica. Material eMétodos: Revisão dos prontuários de todas as crianças com diagnóstico confirmado de S. Alport por biópsia com microscopia eletrônica. Resultados:Vinte e dois pacientes, de vinte diferentes famílias, com idade inicial de 7 ± 6.5 anos, com tempo médio de acompanhamento de 8 ± 8 anos foramestudados. A queixa mais freqüente foi de hematúria macroscópica com antecedente familiar de insuficiência renal crônica (IRC), seguida da de hematúriamicroscópica e antecedente familiar de hematúria . Dezenove casos tiveram evolução pôndero-estatural dentro do canal de crescimento. Hipertensãoarterial e anemia somente foram detectadas nos casos com evolução para IRC e após a sua instalação. Perda auditiva neuro-sensorial foi encontrada aos10 ± 4 anos em 09/22, sendo que todos evoluíram para IRC (p= 0,002). Proteinúria nefrótica surgiu entre oito e 12 anos de idade e somente nos casoscom evolução para IRC (p= 0,002). A média do clearance de creatinina nas faixas etárias de 4 a < 8; 8 a <12; 12 a <16 e nos >= 16 anos foramrespectivamente de 123,0; 107,1; 84,8 e 69,7 ml/min/1.73 m2 . Doze pacientes (seis de cada sexo) evoluíram para IRC classe IV, com idade média de15 ± 4 anos. Conclusões: A presença de hematúria macroscópica e o aparecimento de perda auditiva neuro-sensorial e proteinúria nefrótica forampreditivos de evolução para IRC terminal.

Objective: To present the clinical course of children with Alport Syndrome and determine predictive factors for end stage renal failure. Material e Methods:Revision of charts of patients with Alport Syndrome diagnosed by electronic microscopy of kidney biopsies. Results: Twenty-two patients, from twentydifferent families, mean age of 7± 6.5 years, mean follow-up of 8±8 years were studied. The most frequent finding was macroscopic hematuria inassociation with familiar history of chronic renal failure followed by microscopic hematuria in conjunction with familiar history of hematuria. Nineteen patientshad weight and stature inside growth channel. Hypertension and anemia only were detected in patients that already had chronic renal failure. Neurosensorialhearing loss appeared at the mean age of 10 ± 4 years in 9/22, and all of them developed chronic renal failure (p=0.002). Nephrotic proteinuriaappeared when children were between 8 and 12 year-old, and only in patients that developed chronic renal failure (p=0.002). The mean of creatinineclearance in ages from 4 to < 8 years, 8 to <12 years,12 to <16 years, and >= 16 yearswere respectively 123.0, 107.1, 84.8, and 69.7 ml/min/1.73 m2.Twelve patients (six of each sex) developed class IV chronic renal failure, at a mean age of 15 ± 4 years. Conclusion: Macroscopic hematuria, neurosensorialhearing loss and nephrotic proteinuria were predictable of progression to chronic renal failure in childhood.

Alport syndrome and diffuse leiomyomatosis. Clinical aspects, pathology, molecular biology and extracellular matrix studies. A synthesis.

The Alport syndrome-diffuse leiomyomatosis association can be defined as a hereditary disease of type IV collagen combining features of Alport syndrome (hematuric nephropathy, deafness and ocular abnormalities: anterior lenticonus, maculopathy) and leiomyomatosis involving oesophagus (diffuse type), tracheobronchial tree, and genitals (only in women). This entity is transmitted as an X-linked dominant trait. Mutations of both the COL4A5 and COL4A6 genes, located head to head in Xq22 encoding the alpha 5 and alpha 6(IV) chains are responsible for the abnormalities. Molecular studies have shown deletions of the 5' end of both COL4A5 and COL4A6 including the intergenic region. The breakpoint in COL4A6 is always located within intron 2. Immunohistochemistry has shown significant alterations of basement membranes in the kidney and esophageal leiomyomas. Leiomyomas lack alpha 5 and alpha 6(IV) chains, fibronectin and laminin beta 1 chains in the muscle basement membranes where they are normally expressed. The tumors also show myocyte anomalies: irregular expression of the alpha 5 integrin subunits, and disorganization of actin and desmin filaments. It is hypothesized that a third as yet unknown gene, situated within the large intron 2 in a critical 90 kb region, is responsible for the smooth muscle proliferation. Abnormalities of the basement membranes could destabilize interactions between muscular cells and the extracellular matrix.

Síndrome de epstein primer caso en la literatura nacional / Syndrome of epstein first case in of literature national

Presentamos el primer caso descrito en la literatura nacional de Síndrome de Epstein; el cual está caracterizado por la presencia de trombocitopatía de plaquetas gigantes, glomerulonefritis proliferativa (con hallazgos idénticos a la microscopia electrónica al Sindrome de Aiport) y sordera neurosensorial

Enfermedad de Alport y hematuria recidivante: estudio comparativo y revisión de la literatura / Alport disease and recurrent hematuria: comparative study and review of the literature

Se estudian 10 casos de nefropatías con patología de la membrana basal (M.B.), recibidas en la Fundación Jiménez Díaz. Seis corresponden a Enfermedad de Alport (EA), uno a Nefropatía Familiar Benigna (H.F.B.) y tres a Hematuria Recidivante (H.R.) no urológica. Se realiza una valoración clínico-evolutiva, y los hallazgos histológicos y ultraestructurales en ocho de ellos mediante Indices Morfológicos de actividad y cronicidad (valor númerico). Resultados: Encontramos engrosamiento predominante de la membrana basal en EA, excepto en uno de los casos que tuvo laminación extensa y poco compromiso de la función renal. La HFB mostró adelgazamiento extenso y uniforme (media de 213 nm., y espesor mínimo de 120 nm.). Las HR presentaron engrosamiento e irregularidades de la MB, ninguno presentó laminación y uno adelgazamiento y ruptura. Conclusiones: La relación encontrada con la función renal permite concluir que el Indice morfológico puede ser útil para la valoración de los pacientes con Nefropatías hereditarias, sobre todo, aquellas de naturaleza progresiva

Renal interstitial foam cells are macrophages.

Immunohistochemical studies on renal biopsies from eight patients with various types of glomerulonephritis showed that the interstitial foam cells belonged to the monocyte-macrophage lineage. There was a strong association between hypercholesterolaemia and the presence of renal interstitial foam cells.

Sindrome de Alport-Perkoff / Alport-Perkoff syndrome

Los autores presentan 3 hermanos que padecen de este síndrome con alteraciones renales y audiológicas, haciendo una prolija descripcion de las manifestaciones clínicas que presentan y de los exámenes complementarios realizados Se hace una descripción de las diversas teorías etiopatogénicas, así como el cuadro clínico, dando enfasis a las manifestaciones audiológicas y sobre todo de la evolución de esta enfermedad. También se describen las alteraciones anátomo-patológicas y se concluye con el tratamiento propuesto para este síndrome.

The authors present/display 3 brothers that suffer of this syndrome from renal and audiológicas alterations, making a tedious description of the clinical manifestations that present/display and of the realised complementary examinations a description of the diverse aetio-pathogenic theories becomes, as well as the clinical picture, giving to emphasis to the audiológicas manifestations and mainly of the evolution of this enfermeda. Also the anátomo-pathological alterations are described and it concludes with the treatment proposed for this syndrome.

Lenticone anterior na Síndrome de Alport: reabilitaçäo visual após facectomia extracapsular em cristalino transparente com implantaçäo de lente intra-ocular de câmara posterior / Anterior lenticonus in Alport's Syndrome: visual rehabilitation after clean lens extracapsular extraction with implantation of a posterior chamber intra-ocular lens

Descriçäo de caso de Síndrome de Alport, em paciente do sexo masculino de 23 anos de idade, com lenticone anterior no olho direito e catarata polar anterior no olho esquerdo, que foi visualmente reabilitado após extraçäo extracapsular com implantaçäo de lente intra-ocular de câmara posterior, em ambos os olhos

[Cryptorchism associated with hereditary nephritis: a 3-generation study in a Puerto Rican family]. / Asociación de criptorquidismo con nefritis hereditaria: estudio de tres generaciones de una familia puertorriqueña.

Twenty three members of a family affected by Alport disease were studied throughout three generation. The incidence of auditory, ocular and hematological manifestation was low. It was found that four males with nephritis also had cryptorchism. This is a documentation of the previously unrecorded occurrence of cryptorchism associated with familiar nephritis. The characteristics of this pedigree are described and a review of the literature is presented.

Asociación de criptorquidismo con nefritis hereditaria: estudio de tres generaciones de una familia puertorriqueña / Cryptorchidism associated with hereditary nephritis: a 3-generation study in a Puerto Rican family

Veintitrés miembros de una familia afectada por nefritis familiar fueron estudiados a lo largo de tres generaciones. La incidencia de manifestaciones auditivas, oculares y hematológicas fue baja. Se encontró que cuatro de los pacientes del sexo masculino con nefritis también presentaron criptorquidismo. En este reporte documentamos la ocurrencia no previamente registrada de criptorquidismo en asociación con la enfermedad de Alport. Se describen las características de la enfermedad en esta familia y se ofrece un repaso de la literatura sobre el tema

Manifestaciones oftalmológicas del síndrome de Alport / Ophthalmologics manifestations of Alport's syndrome

Se presenta un caso de síndrome de Alport, con presencia de lenticono anterior, retinitis pigmentosa atípica y sordera, con biopsia renal característica de nefritis hereditaria. Se discuten las características clínicas del síndrome, con énfasis en las manifestaciones oculares

Nonfamilial hematuria associated with glomerular basement membrane alterations characteristic of hereditary nephritis: comparison with hereditary nephritis.

Characteristic ultrastructural alterations of the glomerular basement membrane (GBM) have been reported in hereditary nephritis and in children without a family history of renal disease. The clinical features, renal biopsy findings, and subsequent course were studied retrospectively in 48 children with such GBM changes to compare findings in those with and without a family history of nephritis and to determine the significance of the GBM changes in patients with nonfamilial disease. All 48 patients had hematuria. For 30, there was hematuria in at least one other member of the family (familial hematuria group); for 18, there was no familial incidence. There were no differences between the two groups with regard to clinical and pathologic findings. At the latest follow-up six boys with familial hematuria and three boys with nonfamilial hematuria had reduced renal function, and nine boys with familial hematuria and four boys and one girl with nonfamilial hematuria had neurosensory deafness. Our study results show that children with these GBM changes, with or without a family history of hematuria, tend to have a progressive course, with frequent occurrence of neurosensory deafness, and that the prognosis is more severe in boys. These observations suggest that such GBM changes in patients with nonfamilial hematuria may represent new mutations for hereditary nephritis.

Síndrome de Alport / Alport's syndrome

Os autores revisam o assunto "Síndrome de Alport" com atualizaçäo bibliográfica. Chamam a atençäo para a heterogeneidade das manifestaçöes clínicas e para a importância da microscopia eletrônica na confirmaçäo do diagnóstico e na contribuiçäo para o entendimento da sua patogênese

Glomerular basement membrane attenuation in familial nephritis and "benign" hematuria.

Lamination of the basement membrane has been considered to be the lesion characteristic of familial nephritis and attenuation to be the lesion of "Benign" familial hematuria. Electron micrographs were reviewed of 57 children who had renal biopsies for persistent hematuria. Attenuation or lamination of the glomerular capillary basement membrane was found in each. Twenty of the 57 children had familial nephritis; 20 had familial hematuria; and 17 had no involved relatives. Follow-up data were available for 14 of 20 children with familial nephritis, 12 of 20 with familial hematuria, and 12 of 17 with sporadic hematuria for 13.6 +/- 6.3, 6.7 +/- 4.6, and 7.0 +/- 4.8 years, respectively, after discovery of hematuria. Five children developed end-stage renal disease: three with familial nephritis, one with familial hematuria, and one with sporadic hematuria. Only two no longer had hematuria. Attenuation of the glomerular capillary basement membrane was seen in every biopsy, whereas lamination was not. Because hematuria and ultrastructural abnormalities were findings shared by all the children, we suggest the possibility that familial nephritis, and familial or sporadic hematuria as defined in this study, may be variations in a spectrum of inherited abnormality or abnormalities in the formation of the glomerular capillary basement membrane.

[Epidemiological study in 4 family units with Alport's syndrome]. / Investigación epidemioloógica en cuatro núcleos familiares con síndrome de Alport.

At the Nephrology Department of the Hospital Infantil de Mexico, four cases of Alport's syndrome. with no relation among themselves, were studied between, June 1978 and November 1979. The diagnosis was based on the presence in the patients, of proteinuria and/or hematuria and in some of the relatives, a history of renal disease, deafness and a variable degree of renal failure; at the renal biopsy examined with electronic microscopy, there were findings compatible with Alport's disease in all four cases. Field studied were carried in the largest possible number of relatives for each family group the clinical viewpoint including measurement of blood pressure, examination of urine with reactive stripes to detect proteinuria and hematuria and audiologic examination. In the group, 130 subjects were studied out of a total of 237; 37% were found affected; 21% complaining of deafness; four female cases (19%) had not reach an uremic condition. From the second group 36 subjects were studied out of 109 members. Fifty per cent were found affected. Three cases had reached an uremic state (15%). Out of the third group with a total of 74 members, 34 cases were studied and 62% were found affected. Two female cases (12%) were complaining of uremia. The third group comprised 60 members and 19 of them were studied finding 13% affected with 2 cases of uremia. There were cases exclusively with renal or auditive involvement or both, at the same time. In our casuistics, most of the cases affected of the kidney or of the auditive apparatus were female patients; likewise, the most severely ill were females. Out of the 106 patients affected of the kidney, there were 11 with uremia and 8 were females. It was noticed that both males and females who were affected, had children of either sex with the same degree of affection, the same as other children with no changes at all; therefore, it is concluded that transmission is by dominant autosomal heredity.