We present the case of a 47-year-old male with no family history of SCD who had been seen in our outpatient clinic since 2002 for proteinuria. In 2006, abdominal ultrasound and magnetic resonance imaging (MRI) showed poor cortico-medullary differentiation and the presence of multiple bilateral parapelvic cysts. In 2007, due to deterioration of renal function with serum creatinine levels of 1.6 mg/dl and proteinuria of 1 g/24 h, it was decided to perform an ultrasound-guided renal biopsy, which revealed changes consistent with moderate-severe chronic interstitial nephritis. In 2009, the patient was admitted due to oedema and dyspnoea on exertion. Examination showed no skin lesions suggestive of skin angiokeratomas. The admission blood test showed a serum creatinine of 1.7 mg/dl and proteinuria of 2.4 g/24 h. Echocardiogram and cardiac MRI findings showed probable cardiomyopathy due to deposition disease. Electromyography showed signs of small fibre neuropathy, with impaired autonomic function. A sweat test failed to pick up sweat after pilocarpine stimulation, and an ophthalmological examination revealed cornea verticillata.

In clinical suspicion of FS, the level of alpha-galactosidase activity in leukocytes and plasma was determined using a fluorogenic substrate 4-methyilumbelliferyl α-D-galactosidase. GLA activity was 0.5 nmol/h/ml (2% of normal) in plasma, and /4.2 nmol/h/mg protein (10.7% of normal) in leukocytes, confirming the diagnosis of EF. Enzyme activity was normal in the patient's relatives studied (mother and sister). Genetic study was performed, genomic deoxyribonucleic acid (DNA) was extracted from dried blood spot and coding gene fragments were amplified by PCR. Direct sequencing of the 7 exons of the GLA gene was performed using a capillary sequencer (ABI PRISM® 310 Genetic Analyzer). The analysis determined that the patient was homozygous for a novel c.1182del (single nucleotide deletion) mutation in exon 7 of the alpha-GLA A gene. The patient's mother and sister were investigated and were negative for this mutation. The remaining siblings were not available for study, but none of them have manifested clinical symptoms associated with the disease to date. The patient has one male child, so the mutation is not transmitted to offspring. Hormone replacement therapy with agalsidase alfa (Replagal®) was initiated. During follow-up, oedema and neuropathic pain improved, but renal function progressively worsened to end-stage renal failure, over a period of 3 years. The patient started haemodialysis, and one year later, he received a living donor kidney graft from his wife. The patient, during post-transplant follow-up, has remained with stable renal function with an estimated glomerular filtration rate of 45 ml/min/1.73 m2, with proteinuria of 200 mg/24 h. Follow-up biopsies were performed at 3 months and 1 year, which showed no Gb3 deposits in the renal tissue. Regarding cardiac evolution, clinically, he presented with the appearance of dyspnoea on exertion, in addition to worsening myocardial fibrosis, assessed by cardiac MRI performed in February 2014. It was decided to change treatment to agalsidase beta (Fabrazyme®), since then.