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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