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Page 18 of 34 West et al. Rare Dis Orphan Drugs J 2024;3:22 https://dx.doi.org/10.20517/rdodj.2023.61

hypertension. Echocardiogram done annually is especially important during hemodialysis to identify these
patients early, enabling timely implementation of additional therapies. While highly sensitive Troponin-I
and -T values are useful for assessing myocardial inflammation in Fabry cardiac disease, the troponin-T
level is also increased due to kidney failure, complicating their interpretation in this setting. Cardiac MRI
can be performed to identify myocardial fibrosis with late gadolinium enhancement, but only with an
approved ACR class II type of gadolinium-based contrast agent to minimize the risk of systemic
nephrogenic fibrosis .
[123]

Kidney transplantation
Men with classical Fabry disease often receive a kidney transplant as they are usually among the younger
[2]
adults starting dialysis at an average age of 42 years . Kidney transplant graft survival and patient survival
[124]
in Fabry disease are similar to those of patients transplanted for other nephropathies . There is no
evidence that Fabry disease recurs in the renal allograft in a significant manner. There are a few reports of
[124]
benign endothelial glycosphingolipid deposits . Fabry males can receive a living-related transplant with
the caveat that neither their mother nor sister, as Fabry heterozygotes, should donate to them [125,126] . ERT is
well tolerated by renal transplant recipients .
[127]

Sertraline-induced phospholipidosis has caused CKD with proteinuria in a renal transplant patient. Such
[128]
cases are probably underestimated and underreported but could be misdiagnosed as Fabry nephropathy .
There are reports of undiagnosed Fabry patients as deceased donors wherein the transplant kidney showed
[129]
changes of Fabry nephropathy on post-transplant biopsy . In one case, the graft had stable function
12 years later with persistent lamellar bodies but a decrease in the overall Gb3 deposits on repeat biopsy .
[130]
This suggests that α-Gal from the transplant recipient may have some effects on the graft Gb3 burden.

Immunosuppressive therapy
Immunosuppressive therapy with high-dose prednisone has been used to induce remission in Fabry
nephropathy patients who suddenly develop high-grade proteinuria. This does not represent a response of
this metabolic disease to immunosuppression but rather a case of concurrent minimal change disease or
[131]
FSGS usually in children or young adults .
Routine treatment of patients with Fabry nephropathy with immunosuppressive drugs is not recommended
other than for post kidney transplant. It is of interest that immunosuppressive therapy in that situation has
been reported to result in a lower prevalence of neutralizing anti-drug antibodies in adult males receiving
ERT . In addition, the in vivo neutralization of ERT was significantly reduced by this treatment but
[132]
tended to increase as immunosuppression was reduced.

Specific therapy
Before therapy, physicians should always consider the whole clinical picture relevant to an individual. This
includes key affected organ systems, i.e., cardiac, renal, and cerebrovascular, symptoms such as pain and
gastrointestinal manifestations, concurrent medical conditions, and negative impacts on mental health and
quality of life.

Fabry-specific therapies available in Canada include: (1) ERT with agalsidase-beta (Fabrazyme®, Sanofi-
[133]
Aventis LLC) approved for patients with Fabry disease aged ≥ 8 years ; (2) ERT with agalsidase-alfa
(Replagal®, Takeda Pharmaceuticals) approved for use in patients with Fabry disease, with dosage
recommendations for ages 7-65 years ; and (3) Migalastat (Galafold®, Amicus Therapeutics), an oral
[134]