Sudden onset of nephrotic syndrome in an asymptomatic Fabry patient: a case report

Figures & data

Figure 1. Pedigree of the kindred with Fabry disease. Y: years old.

Figure 2. Skin injury. (A) Skin angiokeratoma (arrow) on the back of the proband; (B) Skin angiokeratoma (arrow) on the lower abdomen of the proband’s younger brother.

Table 1. The laboratory results of the proband.

Item	Proband	Normal range
Age (years)	32	–
Gender	Male	–
Proteinuria	3+	Negative
24 h urine protein (g)	6.38	<0.15
Serum urea (mmol/L)	6.21	3.1–8.0
Serum creatinine (µmol/L)	95	41–73
eGFR (mL/min/1.73 m^2)	90.9	≥90
Serum albumin (g/L)	28	40–55
Total cholesterol (mmol/L)	6.5	0–5.18
Triglycerides (mmol/L)	2.96	0–1.7
High-density lipoprotein (mmol/L)	1.05	1.04–1.55
Low-density lipoprotein (mmol/L)	3.65	0–3.37
Hemoglobin (g/L)	142	130–175
Immunoglobulin A (g/L)	2.06	0.7–4.0
Immunoglobulin G (g/L)	4.4	7–16
Immunoglobulin M (g/L)	0.73	0.4–2.3
Immunoglobulin E (IU/mL)	22.27	0–100
C3 (g/L)	1.08	0.7–1.4
C4 (g/L)	0.155	0.1–0.4
ANAs	Negative	Negative
ANCA	Negative	Negative
HBs-Ag	Negative	Negative
HCV-Ab	Negative	Negative
α-gal activity in WBC (nmol/h/mg)	0.31	31.30–51.00

eGFR was calculated using the CKD-EPI equation. ANAs: anti-nuclear antibodies; ANCA: antineutrophil cytoplasmic antibody; HBs-Ag: hepatitis B virus surface antigen; HCV-Ab: hepatitis C virus antibody.

Figure 3. (A) (HE 400×) and (B) (PAS 400×): Light microscopy showed normal glomerular volume, well-opened capillary loops, and mild segmental mesangial widening with increasing mesangial matrix. Swollen podocytes with abundant, foamy, clear cytoplasm were observed (arrow); mild chronic tubulointerstitial lesions and mild acute lesions were presented, along with flattened tubular epithelial cell and brush border loss (asterisk). (C and D) By electron microscopy, glomerular capillary loops were well-opened and basement membranes were of normal thickness. Extensive foot process fusion (black arrow) with microvillus transformation was observed in the podocyte. And osmiophilic lamellar inclusions were abundantly presented in the podocyte cytoplasm, some of which showed appearance of zebra body (white arrow).

Table 2. Laboratory and clinical data of nine cases with NS in FD patients.

Ref	Gender	Age (years)	Urinary protein levels	α-gal activity	Genetic variant	Clinical manifestations	Treatment	Prognosis	Family history
Fujisawa et al. [20]	M	67	11.13 g/gCr	Leukocyte 1.0 nmol/h/mg protein (normal range: 20–80 nmol/h/mg protein)	GLA gene variant: M296I	Rapid onset of NS and renal dysfunction	Steroids, cyclosporine A and ERT	He sustained nephrotic syndrome remission	–
Reyes Marin et al. [21]	M	22	7–12 g/24 h	Serum 0.18 nmol/h/ml (normal range: >128 nmol/h/ml)	NA	Intermittent weakness, acroparesthesias, hypohidrosis, heavy proteinuria, hypertension and moderate renal failure	NA	NA	–
Majima et al. [22]	F	36	2–4 g/24 h	Leukocyte 31.1 nmol/h/mg (normal range: 21.2–53.1 nmol/h/mg); Culture skin fibroblasts 3.1 nmol/h/mg (normal range: 18.3–29.5 nmol/h/mg)	NA	NS, lupus nephritis	NA	NA	–
Thamboo et al. [23]	F	30	1.8 g/24 h	Normal	NA	NS	Steroids, cyclosporin and cyclophosphamide	steroid-dependent	–
Inagaki et al. [24]	F	15	4 g/24 h	Culture skin fibroblasts 68.4 nmol/h/mg protein (normal control: 49.2 nmol/h/mg protein)	WT	Edema and proteinuria, Hypoproteinemia and hypercholesterolemia	steroid therapy	Proteinuria disappared and complete remission has been maintained	–
Fischer et al. [25]	M	39	2–4 g/24 h	NA	NA	NS, cardiomyopathy, skin rash and hypertension	NA	NA	NA
Fischer et al. [25]	F	73	3.6 g/24 h	NA	NA	NS, type II diabetes with neuropathy, mild hypertension	NA	NA	NA
Zarate et al. [26]	M	16	3.5 g/ gCr	Plasma 0.2 U/ml; leukocyte 0.6 U/mg (normal range: NA)	GLA gene variant: W226 X	episodic hand and foot pain, emesis, abdominal pain, facial swelling, hypertension, moderate aortic insufficiency with mild aortic root dilatation, hypertension, acute NS and ARF	Calcium channel blocker, steroid, ERT	His proteinuria became undetectable and his NS has a sustained remission.	+: several relatives affected
Zhou et al. [27]	M	30	3.6 g/24 h	Serum 18.91 nmol/mL/mg/h (normal range: > 37 nmol/mL/mg/h)	GLA gene variant: (GLA-E07.1286_*7 del	bilateral lower extremity edema and foamy urine	ARB, statin and diuretics	His proteinuria has not significantly decreased.	NA

M: male; F: female; NS: nephrotic syndrome; −: negative; NA: not available; WT: wildtype.

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