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Page 397 Chandramohan et al. J Transl Genet Genom 2024;8:394-404 https://dx.doi.org/10.20517/jtgg.2024.38

Plasma GL-3 and Lyso GL-3 samples were collected in a heparin tube. Analysis was performed in one of
two participating labs: the Genetic Testing Laboratory at the Department of Genetics and Genomics
Sciences, Mount Sinai School of Medicine, and Genzyme, a division of Sanofi. Both plasma and Leukocyte
enzyme activity were evaluated. GL-3 was extracted from the plasma with chloroform/methanol and
purified by solid-phase chromatography. Total GL-3 was measured by liquid chromatography/tandem mass
spectrometry. Plasma Lyso GL-3 was extracted from plasma by protein precipitation and lipid removal
filtration. The extract was separated by reverse-phase liquid chromatography and Lyso GL-3 was quantified
using a tandem mass spectrometer. The reference range for GL-3 was < 7.0 µg/mL, and the reference range
for Plasma Lyso GL-3 was < 5.0 ng/mL.

Transthoracic resting echocardiogram for left ventricular hypertrophy
The size and pressure of the left and right ventricles and atria, the structure and function of the mitral,
tricuspid, aortic, and pulmonary valves, and the root and dimensions of the great vessels were all assessed
using MMode/2D measurements.

RESULTS
Thirteen adult female patients with confirmed Fabry disease diagnosis who underwent kidney biopsies at
the University of Alabama at Birmingham between 2000 and 2020 were reviewed in retrospect. All thirteen
participants were unrelated and had prior genetic testing to identify the α-galactosidase A gene mutation.
The ages ranged between 17 and 48 years, and the mean age was 31.7 years. There was no prior history of
hypertension or diabetes mellitus. Three patients (3, 9, and 10) had missense mutations, while others had
classic nonsense mutations.

Acroparesthesia was present in 7 patients, hyperhidrosis in 2 patients, and gastrointestinal symptoms in 5
patients. Eye changes and angiokeratomas were present in 4 patients. The clinical characteristics of the 13
female Fabry disease patients are summarized in Table 1. At the time of kidney biopsy, all the patients had
creatinine in the near normal range (reference range: 0.7-1.2 mg/dL). The median serum creatinine was 0.7
mg/dL (0.5-1.2). The eGFR was normal to mildly sub-normal and eGFR values were calculated by the
2
2
CKD-EPI equation. The mean eGFR was 100 mL/min/1.73m and ranged from 56 to 130 mL/min/1.73m .
The median UPCR was 0.16g/g (0.04-0.51). None of the patients were on Renin Angiotensin Aldosterone
System inhibitors at the time of their biopsy. Plasma Lyso GL-3 was undetectable for the majority; three
patients had detectable but minimally elevated Lyso GL-3 levels (reference range: < 5.0 ng/mL). GL-3 was
below 3 µg/mL for all patients (reference range: < 7.0 µg/mL). Left ventricular hypertrophy was present in 2
patients and echocardiogram data were unavailable in 3 patients. Sixty-nine percent of the patients (9/13)
were started on enzyme replacement therapy after the biopsy.

Kidney biopsy
On light microscopy, there was global glomerular sclerosis seen in 3 patients, involving 2 glomeruli in one
patient and 1 glomerulus in two patients. There was minimal focal glomerular sclerosis seen on light
microscopy in 1 patient. All the patients had enlarged parietal epithelial cells with a vacuolated appearance.
Interstitial fibrosis and tubular atrophy (IFTA) is absent in all the patients. Minimal hyaline arteriopathy
was seen in 61.5% (8/13 patients) and was absent in the others. The average score grading vacuolization of
podocytes per the ISGFN was 2.2 (maximum score of 3); 38% of patients (4/13 patients) had ≥ 50% foot
process effacement. The mean score of the biopsies was 2.43.