Researchers Urge Genetic Testing for Autosomal Dominant Alport Syndrome

A significant number of patients with a family history of kidney disease that was difficult to diagnose have autosomal dominant Alport syndrome, according to a study from Japan.

The study, published in the journal Nephrology, suggests that genetic testing is crucial in patients with familial kidney disease who are difficult to diagnose using clinical or tissue biopsy examinations.

Researchers from the Toranomon Hospital in Japan noted that rates of autosomal dominant Alport syndrome are increasing, suggesting that the condition might not be as rare as previously believed.

One cause of Alport syndrome are mutations in the COL4A5 gene, which leads to a form of the disease that mainly affects boys because the gene sits on the X chromosome (men have only one X chromosome). Mutations in the COL4A3 and COL4A4 genes cause other forms of Alport syndrome.

Autosomal recessive disease is found when two faulty gene copies are necessary for disease to develop, while autosomal dominant disease is caused by a mutation in only one gene copy.

People with autosomal dominant Alport syndrome typically have slower progression of kidney disease and less hearing and eye abnormalities than X-linked Alport syndrome.

But studies show that mutations in only one gene copy of the COL4A3 and COL4A4 genes can also be found in patients diagnosed with thin basement membrane nephropathy, a non-progressive kidney abnormality.

The study, “Autosomal dominant form of type IV collagen nephropathy exists among patients with hereditary nephritis difficult to diagnose clinicopathologically,” examined the COL4A genes in 19 patients who were difficult to diagnose using clinical examinations and kidney tissue analysis.

They all had blood and protein in their urine, and some had kidney failure. Analyses of kidney tissue had shown abnormalities but normal levels of the COL4A5 protein.

The results showed that 69% of patients had mutations in one gene copy of either COL4A3 or COL4A4. X-linked Alport syndrome was diagnosed in 25% of the group, and one patient did not have mutations in any of the COL4A genes.

Among those with autosomal dominant Alport syndrome, two had hearing loss, but none had eye problems.

These findings support earlier studies indicating that this form of Alport syndrome is more common than researchers previously believed.