FABRY DISEASE: DIAGNOSIS OF A RARE DISORDER

Abstract

Fabry disease (FD) is an X-linked inborn error of glycosphingolipid metabolism due to the deficiency of α-galactosidase A. The progressive accumulation of globotriaosylceramide (Gb3), particularly in the vascular endothelium, leads to renal, cardiac, and cerebrovascular manifestations and early death. Clinical manifestations include the onset of pain and paresthesias in extremities, angiokeratoma and hypohidrosis during childhood or adolescence. Proteinuria
and lymphedema occur with increasing age. Severe renal impairment leads to hypertension and uremia. Death usually occurs due to renal failure or cardiac or cerebrovascular disease. Disease presentation may be subtle, and its signs and symptoms are often discounted as malingering or are mistakenly attributed to other disorders, such as rheumatic fever, neurosis, multiple sclerosis, lupus, or petechiae. We present a 46-year-old man who since adolescence has suffered from painful acroparesthesia, disseminated skin angiokeratomas, hypohidrosis and heat intolerance. He was submitted to a thorough investigation with different specialists, but never reached a diagnosis. He started hemodialysis 3 years ago and at the moment is in standby for kidney transplantation.
He was enrolled in a Brazilian FD screening and a reduced serum activity of α-galactosidase A (0.0027 nmol/h/mL – reference value 4-22) confirmed the diagnosis of FD. He has angiokeratoma at the bottom area, his echocardiogram demonstrated left ventricular hypertrophy and the family history is very rich, as the patient has 15 siblings. This case represents a very common story for FD patients. They usually spend most of their lives trying to find someone who could understand or explain their suffering. These results indicate that FD may be much more common among male dialysis patients than previously recognized. Subsequently, FD should be considered in every patient with unexplained renal disease, especially when cardiac or cerebral complications suggest an underlying multisystemic disorder. Early diagnosis of FD is important because it allows family studies to identify other affected relatives for genetic counseling and therapeutic intervention.
Keywords: Chronic kidney disease; enzyme replacement therapy; fabry disease;
angiokeratoma corporis diffusum; α-galactosidase; agalsidase; lysosomal diseases, renal dysfunction