Alport syndrome - a rare histological presentation Article January - PDF document

See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/242570108 Alport syndrome - a rare histological presentation Article · January 2010 CITATIONS READS 4 521 8 authors , including: Susana Sampaio Maria do Sameiro Faria University of Porto Centro Hospitalar do Porto 73 PUBLICATIONS 352 CITATIONS 132 PUBLICATIONS 746 CITATIONS SEE PROFILE SEE PROFILE Conceição Mota Centro Hospitalar do Porto 74 PUBLICATIONS 318 CITATIONS SEE PROFILE Some of the authors of this publication are also working on these related projects: Circulatory death organ donation (Maastricht II) with normothermic regional perfusion support View project Predictors of health-related quality of life in end-stage renal disease patients under online hemodiafiltration View project All content following this page was uploaded by Maria do Sameiro Faria on 28 May 2014. The user has requested enhancement of the downloaded file.

CASE REPORT Port J Nephrol Hypert 2010; 24(1): 51-55 Advance Access publication 30 September 2009 Alport syndrome – a rare histological presentation Ariana Afonso 1 , Isabel Valente 1 , Liliana Macedo 1 , Susana Sampaio 2 , Sameiro Faria 1 , Teresa Costa 1 , Elói Pereira 1 , Conceição Mota 1 1 Paediatric Nephrology Unit, Hospital Maria Pia, Centro Hospitalar do Porto, Portugal. 2 Nephrology Department, Hospital S. João. Porto, Portugal. 04/06/2009 Received for publication: 21/09/2009 Accepted in revised form: � ABSTRACT associated with neural hearing loss and ocular abnormalities 1-4 . The prevalence of this disease is estimated at approximately 1 in 50 000 live births 5 . Hereditary nephritis or Alport syndrome is a pro- gressive form of glomerular disease that is often Studies carried out since the 1980s have established associated with neural hearing loss and ocular that Alport syndrome is a primary basement mem- abnor malities. The histological changes in Alport brane disorder arising from mutations in genes kidneys are characteristic but not pathognomonic. encoding several members of the type IV collagen protein family 1,6,7 . It is a genetically heterogeneous The presence of crescentic formations is rare. disease with X-linked, autosomal recessive and autosomal dominant variants 1,7 . In approximately 80 We report the case of a 16 -year -old male with a family history of renal disease who underwent renal transplan- percent of patients the disorder is inherited as an tation after progressive renal failure due to Alport syn- X -linked trait, arising from mutations in the COL4A5 gene on the X chromosome 1 . Autosomal recessive drome with crescentic proliferation on renal biopsy. inheritance accounts for about 15 percent of patients with hereditary nephritis 8 . The genetic defect in Although rare, the evidence of crescentic prolif- eration in Alport syndrome has been documented these patients involves the COL4A3 and COL4A4 genes, which are located on chromosome 2 1 . The by some authors. It is difficult to identify its role as a cause or an epiphenomenon of the evolution clinical manifestations are virtually identical to those -linked hereditary nephritis 9,10 . About 5 observed. However, when found in a renal biopsy of classic X its presence can be interpreted as a marker of percent of families have autosomal dominant dis- un favourable outcome and therefore identify patients ease, which arises from heterozygous mutations in the COL4A3 or COL4A4 genes 4,11 . The clinical and at a higher risk of rapid renal function deterioration. pathologic features of this form are similar to those Key-Words: of X-linked disease, although deterioration of renal function tends to occur more slowly 4,12 . Alport syndrome; crescentic proliferation; hereditary nephritis; kidney biopsy. The initial renal manifestation of Alport syndrome is asymptomatic microhaematuria 1 . This usually begins in childhood and is manifested by recurrent � INTRODUCTION or persistent haematuria and proteinuria 13 . Increas- ing proteinuria, hypertension and progressive renal insufficiency occur with time 1 . End-stage renal dis- Hereditary nephritis or Alport syndrome is a pro- gressive form of glomerular disease that is often ease usually presents in males in the second or third 51

Ariana Afonso, Isabel Valente, Liliana Macedo, Susana Sampaio, Sameiro Faria, Teresa Costa, Elói Pereira, Conceição Mota decade, during late adolescence or early adult- hood 1,2,13 . The diagnosis of Alport syndrome is usually sus- pected from the family history of renal failure and deafness 1 , and can subsequently be confirmed or excluded in the majority of cases by the performance of a renal biopsy 1 . On electron microscopy, the earl- iest change is thinning of the glomerular basement membrane (GBM) 14 , which is not pathognomonic 1 . With time, the changes become diagnostic for Alport syndrome, with the development of longitudinal splitting of the lamina densa of the GBM, producing Figure 1 a laminated appearance 1,13 . Although not absolute, Pedigree of family there appears to be a correlation between the sever- The arrow indicates the index patient. Filled dark squares indicate indi- ity of the underlying genetic defect and the severity viduals with Alport syndrome. Filled light circle indicates individual with of the ultrastructural changes 1,13 . The renal histo- haematoproteinuria. logical changes on light microscopy are nonspecific and include focal increases in glomerular cellularity, progressing to glomerulosclerosis, and interstitial infiltrate containing lipid -laden foam cells of uncer- also an older brother with Alport syndrome diag- tain origin 1 . Although described in the literature 15-19 , nosed at the age of seven (Fig. 1). the presence of crescentic formations in Alport syn- drome is rare. The patient presented initially with glomerular microscopic haematuria when he was six months old. There is no specific treatment for Alport syn- Recurrent episodes of macroscopic haematuria were drome 1 . Angiotensin -converting enzyme inhibitors noticed after nine months of age. Haematoproteinu- have been used to retard the progression of the ria was documented at the age of three and he disease 6 , and they are particularly prescribed for started on angiotensin-converting enzyme inhibitor. those patients with proteinuria. Another pharmaco- Long standing haematuria and intermittent proteinu- logical therapy is ciclosporin, which can suppress ria have been documented since then. The immuno- proteinuria and stabilise renal function and histo- logical study was normal, including complement logical changes 20 . Either dialysis or transplantation component levels, antinuclear antibodies, anti GMB can be performed in patients who develop end -stage antibodies and MPO-ANCA and PR3-ANCA. Sen- renal failure 1 . sorineural hearing loss was detected when he was nine, and a hearing aid was provided. He has been The objective of this case report is to present and under regular ophthalmologic surveillance, without discuss the case of a 16 -year -old male with renal significant alterations. He developed nephrotic syn- failure due to Alport syndrome, with crescentic pro- drome at the age of 10 years, with a quantified proteinuria of 99mg/m 2 /hour and a glomerular filtra- liferation on renal biopsy. tion rate (GFR) of 107ml/min/1.73m 2 of body surface area and normal blood pressure, resulting in ciclosporin being introduced. Treatment with ciclosporin was � CASE REPORT maintained for four years, with progressive reduction of the dose. He had good response, with decreasing We report a case of a 16 -year -old male who urinary protein excretion and stable creatinine clear- underwent renal transplantation after progressive ance until he was 14. Blood pressure always remained renal failure due to Alport syndrome with crescentic within normal ranges for age and gender. proliferation on renal biopsy. His family history was significant for his mother, who presented in her late At 15 years old, approximately one year after 20s with persistent haematoproteinuria. There was ciclo sporin had been discontinued, sudden 52 Port J Nephrol Hypert 2010; 24(1): 51-55