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RARE DISEASES
Fabry disease in a renal transplant recipient
Although Fabry disease is considered ‘ rare ’, its inheritance , genetics , pathophysiology and systemic manifestations are very well understood .
Cytoplasmic vacuoles contain electron-dense material in parallel arrays ( zebra bodies ) and in concentric whorls ( myelin figures ).
Our patient is a 47-year-old male who presented to the renal unit with end stage renal disease in 2005 . The aetiology of his kidney disease was unknown at that time although he did have hypertension that was thought to be secondary to his renal failure . The patient had no history of diabetes and was commenced on tegretol for a severe painful peripheral neuropathy that had developed before he required dialysis . He also reported no family history of any chronic illnesses before he was commenced on haemodialysis .
An ultrasound of his kidneys revealed that they were small and shrunken . In 2007 at age 37 he received a live related allograft from his sister who was a year older than him . The donor had no known medical illnesses and was considered suitable by the transplant team . The HLA matching was 4 / 6 and they both had previous exposure to cytomegalovirus infection .
The induction agent was an interleukin 2 receptor blocker and the patient developed immediate diuresis post-transplant . Maintenance immunosuppression consisted of tacrolimus , mycophenolate mofetil and prednisone .
After one month after the transplant he was admitted with allograft dysfunction . The main consideration was of an acute rejection and a transplant biopsy was done .
The light microscopy features were in keeping with an acute cellular rejection ( Type II A ). However , when the electronic microscopy was done myelin bodies were found and on reappraisal of the histology the features were in keeping with a glycogen storage disease .
These inclusions composed of concentric layers with a periodicity of 3.5 to 5 nm and with an onionskin appearance , are considered a hallmark of glycolipid storage disorders .
The recipient and donor then underwent an enzyme assay and genetic testing to exclude Fabry disease . The donor ’ s Alpha-galactosidase level : 85.21pmol / spot * 20h ( normal 160- 2000pmol / spot * 20h ) and the diagnosis was confirmed on molecular genetic testing . The recipient ’ s Alpha-galactosidase level was 25 . 88pmol / spot * 20h .
( Normal : 160-2000pmol / spot * 20h ) which was sufficient to confirm the diagnosis in a male patient .
Both patients continue to be followed up in our transplant clinic . The transplant team is in the process of assisting the donor to receive enzyme replacement therapy . Through a combined effort of the transplant team , we were able to get the recipient enrolled onto a international charity programme which initially funded enzyme replacement therapy for Fabry disease from 2010 onwards . He has subsequently obtained health insurance and the enzyme replacement therapy was continued for the past seven years .
His other comorbidities that he developed include dyslipidaemia , a urethral stricture and a benign gastric polyp , all of which have been adequately managed . His peripheral neuropathy also improved on enzyme replacement therapy . He has not suffered any of the dreaded complications of Fabry disease and is symptom free . The graphs represent his proteinuria and renal function .
The patient was commenced on enzyme replacement therapy at a dose of 1mg / kg every two weeks since 2010 .
The slide ( Figure 1 ) indicates that there has been approximately 1 ml / min / year decrease in renal function over the past 10 years .
The donor has a creatinine clearance ( Figure 2 ) of 99 ml / min in 2016 and her 24 hour protein
20 | May 2017
The Specialist Forum | Vol . 17 No . 4