UKidney's Ask the Experts

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  2. Renal Transplantation
  3. Tuesday, 13 February 2018
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We transplanted a kidney from a deceased donor last week. The kidney was slow to recover in one of the recipients (we received both kidneys) and that recipient was biopsied. The pathology showed renal phospholipidosis. Our pathologist was wondering about Fabry disease. I suppose we could do genetic testing on the renal biopsy. The donor had no known Fabry. But suppose the donor was a mosaic, would the kidney be at risk from low alpha-gal activity? I’m assuming the kidney will recover from the ATN, but would there be a role for enzyme replacement afterwards if the kidney does have Fabry phenotype?
Responses (1)
Michael West
Accepted Answer
Complicated situation. Sounds like a reportable case.

Presumably the donor was not taking chloroquine or hydroxychloroquine which can cause phospholipidosis and mimic Fabry disease. If there is some blood left from the donor then that could be tested for Fabry disease with GLA gene analysis this would be the best way to identify a female heterozygote or a male hemizygote. If the donor was male then α-galactosidase activity could be measured in WBCs if frozen. Plasma could also be measured but sample usually has to be fresh to be accurate.

From the mosaic comment, I am assuming that the donor was female. There are case reports of mothers inadvertently donating kidney to affected sons who turned out to have Fabry disease. These kidneys show progressive Fabry disease and ultimately fail. In your case you could have  heterozygous mosaic kidney in a non-Fabry recipient. I am unaware that this has ever been reported. The normal α-galactosidase produced in the recipient would theoretically allow for some cross correction in the transplanted kidney but this might be limited especially if there is skewing of the lyonization. Some females could have 80% of the affected X chromosome active and only 20% of the normal X chromosome active in renal cells. However then one would have expected the donor to have exhibited progressive kidney disease. How old was the donor? Average age of starting dialysis is 41 years of age in both men and women with Fabry disease. A good case could be made for enzyme replacement therapy (ERT) in this situation if α-galactosidase deficiency can be demonstrated with a known pathogenic GLA mutation. Also the donor family should ideally be tested for FD as a treatable metabolic disease if confirmed in the donor tissue but there would be issues around confidentiality etc.

You could look for the presence of increased urine Gb3 (substrate) which is supposed to reflect renal origin as well as urine lysoGb3 a major metabolite of GB3 and often present in larger amounts in FD.  These could be positive with either drug induced phospholipidosis or with Fabry disease but would be an important point in favour of ERT. Dr Christiane Auray-Blais in Sherbrooke QC does these assays with tandem mass spectrometry and costs is < $200. There also is now a licensed oral chaperone agent for certain Fabry mutations that enhance or respond-about 20% chance of this in a Canadian patient.
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