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Chandramohan et al. J Transl Genet Genom 2024;8:394-404 https://dx.doi.org/10.20517/jtgg.2024.38 Page 398

Table 1. Genotype and clinical features of female patients with Fabry disease
ERT
No. Sex/Age Mutation Mutation Acroparesthesia Hyperhidrosis Gastrointestinal Eye Angiokeratomas LVH after
category
(y)
symptoms
changes
kidney
biopsy
1 F/46 Classic R227X Y N Y N N N Y
nonsense
2 F/35 Classic R112C Y N Y Y Y Y Y
missense
3 F/35 Classic Q221X Y N N N N N Y
nonsense
4 F/48 Classic W277X - N - - - - -
nonsense
5 F/38 Classic E79X Y N Y Y Y Y Y
nonsense
6 F/31 Classic R277X N Y N N N N N
nonsense
7 F/20 Classic R277X Y N N Y N N Y
nonsense
8 F/17 Classic W236X N N N Y N N Y
nonsense
9 F/24 Classic R227Q N Y Y - N - -
missense
10 F/39 Classic Y207S Y N Y N Y - N
missense
11 F/29 Classic W277X N N N N N N Y
nonsense
12 F/32 Classic R277X Y N N - N N Y
nonsense
13 F/18 Classic R277X N N N N Y N Y
nonsense

Abbreviations: Y: Yes; N: No; LVH: Left ventricular hypertrophy; ERT: Enzyme replacement therapy.

Figures 1 and 2. show the light microscopy. Figures 3 and 4 shows the electron microscopy of a female
patient. The scoring sheet used in evaluating the biopsies can be found in the Supplementary Materials. The
laboratory and the kidney biopsy findings are summarized in Table 2.

DISCUSSION
Our study shows that a significant number of female patients with FD with low Lyso GL-3, low levels of
proteinuria, and creatinine values within the normal reference ranges have histological signs of the disease
on renal biopsy. FD is characterized by the progressive intracellular accumulation of glycolipids, which
resemble myelin primarily in podocytes. This gradual accumulation also occurs in the mesangial,
[15]
glomerular, endothelial, tubular epithelial cells, and arteries . Due to variations in the lyonization of the
X-chromosome, females even with the same mutations can display significant phenotypic variation . In the
[7]
absence of significant Fabry-related symptoms, treatment recommendations for some females without
histology or accurate biomarkers are difficult.

Lyso GL-3 has been used as a biomarker to monitor disease activity and to monitor response to enzyme
replacement therapy. However, it may be less reliable in females due to lower baseline Lyso GL-3 levels .
[16]
Due to these limitations, histology has been a mainstay for assessing FD involvement in oligosymptomatic
[17]
female Fabry patients .