How can we suspect Fabry nephropathy as a nephrologist when we are sitting in front of a patient? Well, first, it will be much more common in males than in females. Second, we should ask about family history of kidney disease, of cardiac disease. Third, we should ask about childhood history of pain, of emergency room visits because of pain during fever episodes.

We should ask about if there a history of lacking the ability to sweat. So these patients will be intolerant to exercise because they lose their ability to sweat. We should ask about skin disease, skin lesions in the genitalia. And then, after asking about family history, after asking about personal history, we should focus on the presentation of the patient.

So this will be young males in general, that they patient with proteinuric kidney disease. And a very characteristic feature-- they may have hypertension or normal blood pressure. Usually, individuals with proteinuric kidney disease, with kidney disease of glomerular injury, they will be hypertensive. Fabry patients may be characteristically hypertensive or normotensive.

So differential diagnosis of proteinuric kidney disease with normal or low blood pressure will include Fabry Disease and amyloidosis. Eventually, as glomerular filtration rate goes down, Fabry patients may develop hypertension, but it is usually milder than hypertension found in patients with a similar degree of renal dysfunction.

Finally what is the most common differential diagnosis? Well, any other proteinuric kidney disease. So diabetes will be quite easy to exclude because glucose levels will be normal. However, any other proteinuric kidney disease may be missed for a Fabry nephropathy. The most common one is focal segmental glomerulosclerosis. Why? Because even if the patient has had a kidney biopsy, if the pathologist is not quite familiar with Fabry Disease, the diagnosis of Fabry disease may be missed.

However, histologically, Fabry patients will have glomerular fibrosis, and the main pathologist use for glomerular fibrosis is glomerulosclerosis. And some glomeruli will be more affected than others, so the histological image will be a histological image of focal segmental glomerulosclerosis.

Always remember that focal segmental glomerulosclerosis is a name in need of a surname. So the meaning of focal segmental glomerulosclerosis is that the pathologist is seeing glomeruli that are dying. They are loose in podocytes, and podocytes have been replaced by fibrosis. So focal segmental glomerulosclerosis, the meaning is, glomeruli are dying. And the key question is, why are glomeruli dying?

So we have a primary focal segmental glomerulosclerosis. We don't know why glomeruli are dying, but we have secondary forms. And one cause of secondary focal segmental glomerulosclerosis is Fabry Disease.

So we should think about Fabry Disease in patients with focal segmental glomerulosclerosis where their surname, the cause of this focal segmental glomerulosclerosis, is not known. Because one potential cause of secondary FSGS, secondary Focal Segmental Glomerulosclerosis, is Fabry Disease.