PMC6942789_01
Pedigree analysis. The patient is indicated by the arrow. Black boxes represent males with Fabry disease; circles with black dots represent females with Fabry disease. Slash indicates deceased.
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fig1
The patient is a white woman who was diagnosed with Fabry disease in 2005 at 28 years of age.Her father had Fabry disease (generation II), and all 3 surviving siblings (all females) also had Fabry disease (generation III) (Figure 1).
Time course of (a) proteinuria and albuminuria, (b) creatinine, and (c) eGFRCKD-EPI. ACR, albumin-to-creatinine ratio; eGFRCKD-EPI, estimated glomerular filtration rate chronic kidney disease epidemiology collaboration; PCR, protein-to-creatinine ratio.
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fig2
The following month, ongoing proteinuria (788 mg/24 h, Figure 2) prompted kidney biopsy, which showed cellular characteristics consistent with existing Fabry disease (Figure 3(b)).
Histology and transmission electron microscopy of kidney biopsy specimens obtained (a) in 2005, one month after birth of first child (second pregnancy) and (b) in 2014, during pregnancy with second child (third pregnancy). AFOG, acid fuchsin orange G; IgA, immunoglobulin A; IgG, immunoglobulin G; PAS, periodic acid-Schiff; TEM, transmission electron microscopy. (a) The first renal biopsy (2005) shows a diffuse, segmentally accentuated mesangial matrix and mesangial cell proliferation (PAS and AFOG) in >50% of the glomeruli, and segmentally obliterated capillary loops adherent to the Bowman's capsule (AFOG). There is dominant segmental C3 deposition (C3) in the absence of IgG and IgA. Podocytes show characteristic lamellar and zebroid bodies by TEM; however, the classical appearance of "foamy" podocytes was less dominant by light microscopy (PAS) due to the segmental nature of the pathological changes. (b) The second renal biopsy (2014) shows characteristic foamy macrophages (PAS and AFOG) as well as segmental mesangial matrix and mesangial cell proliferation. Dominant C3 deposits (C3) correspond to mesangial electron dense deposits (*) by TEM (right) while almost all podocytes contain lamellar and zebroid inclusion bodies (a).
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fig3
Because the patient had complement C3 staining in her kidney biopsy specimens (Figure 3), serologic and genetic complement analyses were performed.
PMC6942789_02
Time course of (a) proteinuria and albuminuria, (b) creatinine, and (c) eGFRCKD-EPI. ACR, albumin-to-creatinine ratio; eGFRCKD-EPI, estimated glomerular filtration rate chronic kidney disease epidemiology collaboration; PCR, protein-to-creatinine ratio.
CRIOG2019-1030259.002.jpg
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fig2
The following month, ongoing proteinuria (788 mg/24 h, Figure 2) prompted kidney biopsy, which showed cellular characteristics consistent with existing Fabry disease (Figure 3(b)).
Histology and transmission electron microscopy of kidney biopsy specimens obtained (a) in 2005, one month after birth of first child (second pregnancy) and (b) in 2014, during pregnancy with second child (third pregnancy). AFOG, acid fuchsin orange G; IgA, immunoglobulin A; IgG, immunoglobulin G; PAS, periodic acid-Schiff; TEM, transmission electron microscopy. (a) The first renal biopsy (2005) shows a diffuse, segmentally accentuated mesangial matrix and mesangial cell proliferation (PAS and AFOG) in >50% of the glomeruli, and segmentally obliterated capillary loops adherent to the Bowman's capsule (AFOG). There is dominant segmental C3 deposition (C3) in the absence of IgG and IgA. Podocytes show characteristic lamellar and zebroid bodies by TEM; however, the classical appearance of "foamy" podocytes was less dominant by light microscopy (PAS) due to the segmental nature of the pathological changes. (b) The second renal biopsy (2014) shows characteristic foamy macrophages (PAS and AFOG) as well as segmental mesangial matrix and mesangial cell proliferation. Dominant C3 deposits (C3) correspond to mesangial electron dense deposits (*) by TEM (right) while almost all podocytes contain lamellar and zebroid inclusion bodies (a).
CRIOG2019-1030259.003.jpg
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fig3
Because the patient had complement C3 staining in her kidney biopsy specimens (Figure 3), serologic and genetic complement analyses were performed.
PMC6942789_03
Fetal MRI (coronal plane) during pregnancy at 29 weeks' gestation. MRI, magnetic resonance imaging. Images presented with patient permission.
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fig4
At 29 weeks' gestation, magnetic resonance imaging indicated normal fetal development (Figure 4).
PMC6942789_04
Histology and transmission electron microscopy of kidney biopsy specimens obtained (a) in 2005, one month after birth of first child (second pregnancy) and (b) in 2014, during pregnancy with second child (third pregnancy). AFOG, acid fuchsin orange G; IgA, immunoglobulin A; IgG, immunoglobulin G; PAS, periodic acid-Schiff; TEM, transmission electron microscopy. (a) The first renal biopsy (2005) shows a diffuse, segmentally accentuated mesangial matrix and mesangial cell proliferation (PAS and AFOG) in >50% of the glomeruli, and segmentally obliterated capillary loops adherent to the Bowman's capsule (AFOG). There is dominant segmental C3 deposition (C3) in the absence of IgG and IgA. Podocytes show characteristic lamellar and zebroid bodies by TEM; however, the classical appearance of "foamy" podocytes was less dominant by light microscopy (PAS) due to the segmental nature of the pathological changes. (b) The second renal biopsy (2014) shows characteristic foamy macrophages (PAS and AFOG) as well as segmental mesangial matrix and mesangial cell proliferation. Dominant C3 deposits (C3) correspond to mesangial electron dense deposits (*) by TEM (right) while almost all podocytes contain lamellar and zebroid inclusion bodies (a).
CRIOG2019-1030259.003.jpg
PMC6942789_04_CRIOG2019-1030259.003.jpg
fig3
Because the patient had complement C3 staining in her kidney biopsy specimens (Figure 3), serologic and genetic complement analyses were performed.