Women with X-linked Alport syndrome may develop severe disease progression. But the type of mutation a patient carries does not predict the disease’s severity, and physicians should pay careful attention while monitoring and treating women with X-linked Alport syndrome, according to a study from the Kobe University Graduate School of Medicine in Japan.
Men most often develop X-linked Alport syndrome because the COL4A5 gene, which causes the syndrome when it is mutated, sits on the X chromosome, and men have only one copy. But because one of the two X chromosomes is inactivated in women’s cells, women also may develop the disease. However, information about the rates and disease course of X-linked Alport syndrome in women is lacking.
This study, titled, “Natural History and Genotype–Phenotype Correlation in Female X-Linked Alport Syndrome,” published in the journal Kidney International Reports, set out to fill in some of the knowledge gap in Japan’s Alport syndrome population.
In a group of 275 women with genetically confirmed X-linked Alport syndrome and 61 affected women family members, the majority — 72.6% — had an abnormal amount of protein in the urine, a condition known as proteinuria, the study found. The median age at which these women developed proteinuria was 7.
Thirty-three women developed end-stage kidney disease. They lived an average of 65 years. Fifteen percent reached end-stage kidney disease by the age of 40. Only 1.5% had eye problems and 5.5% had hearing loss, which are typical of Alport syndrome.
Only patients who developed proteinuria at a young age were treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, researchers found. None of the older patients, including those with end-stage kidney disease, received such treatment.
Looking at the specific mutations, the team found no links to disease severity or the age at which patients reached end-stage disease. They also could not relate the severity of kidney disease to the presence or absence of hearing loss.
The team also performed an analysis to look for other genes that could potentially explain why some women had more severe disease progression. With the exception of one woman, who also had a mutation in the Alport-related COL4A3 gene, they found no so-called modifier genes.
“It, therefore, seems likely that the mechanisms determining the severity of female XLAS are multifactorial,” researchers wrote.
Because women do not always have a mild form of the disease, it is crucial for doctors to pay close attention to the course of the disease in women with X-linked Alport syndrome, researchers concluded.