Alport syndrome - a rare histological presentation

Iranian Journal of Pathology

Pediatric Nephrology, 1987

Case Report , 2023

Alport’s syndrome is a type of inherited disorder of the basement membrane characterized by a spectrum of phenotypes ranging from progressive renal injury to varied extrarenal manifestations comprising auditory and ocular abnormalities. Here in, we present a 3-year-old child born out of nonconsanguineous marriage who presented with fever, intermittent microscopic haematuria, and recurrent gross haematuria, proteinuria with normal auditory brainstem response and ocular slit lamp examination findings. Renal biopsy yielded normal light microscopy and immunofluorescence study whereas minimal changes in the glomerular basement membrane (GBM) collagen were detected on electron microscopy, suggesting possibilities of Alport’s syndrome. Ultrasonographic renal imaging yielded the presence of bilateral medullary nephrocalcinosis. Angiotensin converting enzyme inhibitors along with angiotensin receptor blockers were used to curb the disease progression. A final clinical exome sequencing corroborated the phenotype with a diagnosis of Alport’s syndrome type-1 linked to a novel pathogenic variant c.1892dup (p.Gly632ArgfsTer2) showing hemizygous single base pair insertion/duplication in COL4A5 gene. To the best of our knowledge, this unusual association of Alport’s syndrome with medullary nephrocalcinosis has not been reported worldwide in any previous medical literature making this report a primi one.

portuguese journal of nephrology and hypertension, 2017

Introduction: Alport syndrome is a glomerular genetic disease progressing to chronic renal failure associated with deafness and ocular changes. Clinical presentation is usually in the first decade of life with microscopic haematuria and/or persistent proteinuria without hypertension or renal dysfunction. Case Report: Male, 4.5 years old, with an acute nephritic syndrome characterized by macroscopic haematuria, oedema, non-oliguric acute renal failure (maximal urea and creatinine of 25mmol/L and 150μmol/L, respectively), anaemia and proteinuria. Blood pressure normal. Normal immunoglobulins and complement fractions; anti-neutrophil cytoplasmic antibody, anti-nuclear antibody and anti-basal membrane antibody negative. History of recurrent episodes of macroscopic haematuria since the age of eighteen months associated with respiratory infections. No family history of renal disease or deafness. Renal biopsy showed proliferative glomerulonephritis with extracapillary crescentic activity, ...

BMJ case reports, 2014

Alport syndrome (AS) is a heterogeneous basement membrane disease characterised by haematuria with progressive hereditary nephritis, high-frequency sensorineural hearing loss (SNHL) and pathognomonic ocular lesions. It is one of the spectra of diseases representing hereditary nephritis, which inevitably leads to end-stage renal disease (ESRD). Microscopic or frank haematuria persistent from childhood constitutes the clinical clue for its early recognition. It occurs as a result of genetically inherited or de novo mutations in type IV collagen genes. The most common mode of inheritance is X-linked and men are more severely affected. We report a case of a young woman, in her fourth decade of life presenting with overt nephropathy, having persistent haematuria associated with SNHL and lenticonus with dot and fleck retinopathy on detailed clinical examination, diagnosed as a previously undetected case of Alport syndrome.

Nephrology Dialysis Transplantation, 1996

2018

In a previous issue of this journal, Neves et al.1 reported the occurrence of a severe, normocomplementamic, acute nephritic syndrome at age 41⁄2 years, in a boy with past medical history of self-limited episodes of macroscopic haematuria associated with respiratory infections, who was eventually diagnosed with Alport syndrome (AS) more than 10 years afterwards. The reported baseline laboratory data were unremarkable, except for significantly elevated serum creatinine (sCr), microscopic haematuria with nephrotic range proteinuria, and severe anaemia.

Pediatric Nephrology, 2005

The alleged dominance of diffuse attenuation of the glomerular basement membrane (GBM) in young children and females with Alport's Syndrome (AS) suggests that it might be the initial ultrastructural manifestation of type IV collagen defects. We carried out a 'blind' review of 130 renal biopsies obtained from 100 patients with AS, emphasizing the electron microscopy changes, and related the findings to the clinical presentation and outcome. The intracapillary distribution of (1) thickened, (2) attenuated and (3) normal GBM was assessed individually as: none (grade 0), <25% (grade 1), 25-50% (grade 2) and >50% (grade 3). Deafness was defined as persistent loss of > or =30 dBs. Proteinuria was measured as protein/creatinine ratios in early morning urine. Heavy proteinuria (> or =200 mg/mmol) correlated significantly with the presence of segmental and global glomerulosclerosis and foam cells. Comparing grades 0+1 vs. 3 GBM changes, using a 2x2 chi(2) test, there were significant correlations between grade 3 GBM thickening and male sex (P =0.005), heavy proteinuria (P =0.02) and deafness (P <0.001). GBM thickening did not correlate with age at the initial biopsy, but repeat biopsies demonstrated increasing thickening with age. The grades of GBM attenuation did not correlate with either age at biopsy or sex. In 11 biopsies with atypical lamina densa changes in thickened GBM segments, there were no differences in clinicopathological correlations compared with classical biopsies. Our data indicate that diffuse GBM attenuation can be an ultrastructural variant of the Alport nephropathy, but do not support the contention that it is the initial lesion.

The Open Urology & Nephrology Journal, 2019

Anti-Glomerular Basement Membrane (anti-GBM) crescentic glomerulonephritis developing in an allograft is a rare phenomenon. A patient with Alport syndrome receiving a renal transplant is at risk of developing anti-GBM glomerulonephritis, due to the absence of normal COL4α3, COL4α4 and COL4α5 trimer of the collagen network. Two unique challenges with planning kidney transplant in such a patient include- ideal donor selection; and risk of developing anti-GBM nephritis. We report a case of post-transplant anti-GBM crescentic glomerulonephritis in a female recipient with unknown native kidney disease who was diagnosed with Alport disease when she presented with hematuria and proteinuria nearly 2 years postrenal transplant. Allograft outcome in our case was unfavourable, patient reaching end-stage kidney disease within 6-month of diagnosis. The patient remains on continuous ambulatory peritoneal dialysis and currently active on the deceased donor transplant waiting list.

Pediatric Nephrology, 2011