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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 402

Figure 4. Electron microscopy of the kidney biopsy of a female patient. The glomerulus shows lamellated lipid inclusions (myeloid
bodies) in podocytes (yellow arrows).

in the cohort may have renal involvement. Kidney biopsies are therefore helpful in such cases, as they not
only confirm the presence of GL-3 accumulation, but also assess the extent of its impact on other structures,
such as podocytes, in addition to demonstrating IFTA and other structural changes.

Although kidney biopsies are valuable in establishing a baseline in FD, females with classic symptoms such
as angiokeratomas or elevated Lyso GL-3 may not require one. We recommend that in cases with positive
biomarkers, the necessity of a kidney biopsy should be carefully considered and treatment regimen should
be tailored with the help of experienced nephrologists. Based on our experience, we also recommend that in
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the presence of a significant decline in eGFR > 3 mL/min/1.73m per year, a kidney biopsy should be
considered to evaluate other underlying pathologies.

Currently, three different enzyme replacement therapies (ERTs) and one pharmacological chaperone are
approved for the treatment of FD [25,26] . As more therapeutic options become available, we believe that kidney
biopsies may play a crucial role in guiding treatment choices. In such cases, a baseline kidney biopsy could
be performed prior to treatment initiation, with a follow-up biopsy after 3-4 years to evaluate the need for
adjustments in therapy.

Our study has some limitations. Although we report low Lyso GL-3 levels, at the time of data collection, the
assay for Lyso GL-3 detection had a reference cut-off level of <5 ng/mL. The newer assays currently used
can detect lower levels of Lyso GL-3 of > 0.3 ng/mL. It is possible that the patients in our series with <
5 ng/mL Lyso GL-3 had elevated levels that the newer assays could have detected. Nonetheless, all the
patients had Lyso GL-3 below 5.1 ng/mL.

In conclusion, we report the histopathological findings on the kidney biopsy of 13 female patients with a
known diagnosis of FD but with serum creatinine within the normal reference range and low plasma Lyso
GL-3. The patients in our series also had minimal proteinuria < 0.5 g/g, despite having evidence of podocyte
inclusion bodies and varying degrees of foot process effacement. These findings suggest that kidney biopsy