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The variable course of women with X-linked Alport Syndrome.

Raju P, Cimbaluk D, Korbet SM - Clin Kidney J (2013)

Bottom Line: X-linked Alport syndrome (XLAS) arises from mutations in the COL4A5 gene encoding the α5-chain of type IV collagen and is associated with hematuria, ocular abnormalities and high-tone sensorineural hearing loss.Both developed nephrotic-range proteinuria and progressive renal insufficiency.Additionally, both developed extra-renal manifestations of XLAS.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine , Rush University Medical Center , Chicago, IL , USA.

ABSTRACT
X-linked Alport syndrome (XLAS) arises from mutations in the COL4A5 gene encoding the α5-chain of type IV collagen and is associated with hematuria, ocular abnormalities and high-tone sensorineural hearing loss. Nearly all affected males have decreased kidney function resulting in end-stage renal disease (ESRD) as early as the second decade of life. It was long thought that affected females had a benign outcome; however, in recent decades, it has become quite clear that they too are at risk for developing nephrotic syndrome, decreased kidney function and ESRD. We report two young females presenting with microscopic hematuria and proteinuria diagnosed with XLAS on renal biopsy. Both developed nephrotic-range proteinuria and progressive renal insufficiency. Additionally, both developed extra-renal manifestations of XLAS. The ultrastructural and immunofluorescence features on kidney biopsy were instrumental in making the diagnosis of heterozygous XLAS as neither patient had a family history of AS.

No MeSH data available.


Related in: MedlinePlus

(A) IF micrograph showing staining of normal tissue (positive control) for the alpha 5 chain of type IV collagen. Similar to alpha 3, there is linear staining of the entire GBMs and dTBMs. The alpha 5 chain of type IV collagen also stains Bowman's capsule. (B) On high power, a glomerulus displays weak and segmental positivity for the alpha 5 chain of type IV collagen in the GBMs, and the absence of staining in Bowman's capsule and the dTBMs. Image is from Case Report 1.
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SFT107F3: (A) IF micrograph showing staining of normal tissue (positive control) for the alpha 5 chain of type IV collagen. Similar to alpha 3, there is linear staining of the entire GBMs and dTBMs. The alpha 5 chain of type IV collagen also stains Bowman's capsule. (B) On high power, a glomerulus displays weak and segmental positivity for the alpha 5 chain of type IV collagen in the GBMs, and the absence of staining in Bowman's capsule and the dTBMs. Image is from Case Report 1.

Mentions: Light microscopy (LM) contained six glomeruli, one of which was globally sclerotic. The remaining glomeruli had preserved architecture with delicate basement membranes, patent glomerular capillaries and normal mesangial matrix and cellularity (Figure 1A). Tubular atrophy and interstitial fibrosis involved 5% of the cortex, and interstitial foams cells (Figure 1B) affected 10–15% of the cortex. IF demonstrated weak mesangial staining for IgM (trace–1+) and C3 (trace). The tissue was stained with antibodies to the alpha 1, 3 and 5 chains of type IV collagen. This revealed 1–2+ segmental/mosaic staining of the GBM with the alpha 3 chain of type IV collagen (Figure 2). Staining for the alpha 5 chain of type IV collagen also showed 1+ segmental/mosaic staining of the GBM (Figure 3). There was no staining of the dTBM for either the alpha 3 or the alpha 5 chains of type IV collagen. Electron microscopy (EM) demonstrated diffusely thinned GBMs, measuring 124 nm in average thickness (Figure 4), but there was no lamellation or splitting. Segmental foot process effacement involved 50% of the total glomerular capillary surface area.Fig. 1.


The variable course of women with X-linked Alport Syndrome.

Raju P, Cimbaluk D, Korbet SM - Clin Kidney J (2013)

(A) IF micrograph showing staining of normal tissue (positive control) for the alpha 5 chain of type IV collagen. Similar to alpha 3, there is linear staining of the entire GBMs and dTBMs. The alpha 5 chain of type IV collagen also stains Bowman's capsule. (B) On high power, a glomerulus displays weak and segmental positivity for the alpha 5 chain of type IV collagen in the GBMs, and the absence of staining in Bowman's capsule and the dTBMs. Image is from Case Report 1.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842150&req=5

SFT107F3: (A) IF micrograph showing staining of normal tissue (positive control) for the alpha 5 chain of type IV collagen. Similar to alpha 3, there is linear staining of the entire GBMs and dTBMs. The alpha 5 chain of type IV collagen also stains Bowman's capsule. (B) On high power, a glomerulus displays weak and segmental positivity for the alpha 5 chain of type IV collagen in the GBMs, and the absence of staining in Bowman's capsule and the dTBMs. Image is from Case Report 1.
Mentions: Light microscopy (LM) contained six glomeruli, one of which was globally sclerotic. The remaining glomeruli had preserved architecture with delicate basement membranes, patent glomerular capillaries and normal mesangial matrix and cellularity (Figure 1A). Tubular atrophy and interstitial fibrosis involved 5% of the cortex, and interstitial foams cells (Figure 1B) affected 10–15% of the cortex. IF demonstrated weak mesangial staining for IgM (trace–1+) and C3 (trace). The tissue was stained with antibodies to the alpha 1, 3 and 5 chains of type IV collagen. This revealed 1–2+ segmental/mosaic staining of the GBM with the alpha 3 chain of type IV collagen (Figure 2). Staining for the alpha 5 chain of type IV collagen also showed 1+ segmental/mosaic staining of the GBM (Figure 3). There was no staining of the dTBM for either the alpha 3 or the alpha 5 chains of type IV collagen. Electron microscopy (EM) demonstrated diffusely thinned GBMs, measuring 124 nm in average thickness (Figure 4), but there was no lamellation or splitting. Segmental foot process effacement involved 50% of the total glomerular capillary surface area.Fig. 1.

Bottom Line: X-linked Alport syndrome (XLAS) arises from mutations in the COL4A5 gene encoding the α5-chain of type IV collagen and is associated with hematuria, ocular abnormalities and high-tone sensorineural hearing loss.Both developed nephrotic-range proteinuria and progressive renal insufficiency.Additionally, both developed extra-renal manifestations of XLAS.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine , Rush University Medical Center , Chicago, IL , USA.

ABSTRACT
X-linked Alport syndrome (XLAS) arises from mutations in the COL4A5 gene encoding the α5-chain of type IV collagen and is associated with hematuria, ocular abnormalities and high-tone sensorineural hearing loss. Nearly all affected males have decreased kidney function resulting in end-stage renal disease (ESRD) as early as the second decade of life. It was long thought that affected females had a benign outcome; however, in recent decades, it has become quite clear that they too are at risk for developing nephrotic syndrome, decreased kidney function and ESRD. We report two young females presenting with microscopic hematuria and proteinuria diagnosed with XLAS on renal biopsy. Both developed nephrotic-range proteinuria and progressive renal insufficiency. Additionally, both developed extra-renal manifestations of XLAS. The ultrastructural and immunofluorescence features on kidney biopsy were instrumental in making the diagnosis of heterozygous XLAS as neither patient had a family history of AS.

No MeSH data available.


Related in: MedlinePlus