Variations Between Alport, Pierson Syndromes Explain Kidney Damage Differences

While Alport syndrome and Pierson syndrome are two diseases caused by mutations in genes important for the correct functioning of the kidney’s filtration system, the two diseases have different manifestations.

Understanding what these syndromes have in common and what distinguishes them may benefit the design of targeted therapies for each disease, researchers say.

In the study titled “Alport syndrome and Pierson syndrome: Diseases of the glomerular basement membrane,” published in the journal Matrix Biology, nephrology researchers at Washington University School of Medicine in St. Louis, Missouri, go into great detail when describing both conditions.

Alport syndrome and Pierson syndrome are both caused by mutations in genes that affect the structure and function of the kidney, specifically the glomerular basement membrane (GBM) — a key component of the kidney’s filtration barrier, called the glomeruli.

The GBM, together with two cell types called podocytes and endothelial cells, constitute the filtration barrier of the glomeruli, the structures where the blood is filtered to urine.

The GBM is composed of different proteins, including type IV collagen and laminin, among others. Mutations impairing the function of the genes that provide instructions for making type IV collagen are the underlying cause of Alport syndrome, and alterations in the gene encoding for the protein laminin cause Pierson syndrome.

Mutations in collagen type IV genes —COL4A3, COL4A4, and  COL4A5 — lead to Alport syndrome. Pierson syndrome is caused by mutations in the LAMB2 gene, which encodes a part of the laminin protein. Laminins are the major noncollagen part of basement membranes.

However, while both diseases are characterized by impairments in the structure and function of GBM, the kidney aspects of these diseases are very different.

In Alport syndrome, patients suffer a gradual decline in kidney function that is characterized first by hematuria, the presence of blood in the urine. The presence of abnormal quantities of protein in patients’ urine — called proteinuria — and a sign of kidney damage begins later in the disease course.

In Pierson syndrome, a very rare form of nephrotic syndrome, very high levels of proteinuria are detected at or shortly after birth. Some babies, however, do not show signs of kidney damage until adulthood.

“Deciphering the mechanisms by which the different changes to GBM collagen IV and laminin composition causes these very different manifestations of kidney dysfunction will lead to novel, targeted therapeutic approaches that can improve the lives of patients,” researchers wrote.