Pregnancy May Exacerbate Symptoms of Recessive Form of Alport Syndrome, Case Report Shows

Pregnancy may exacerbate the impact of COL4A4 gene mutations in women who have recessive, or non-symptomatic forms of Alport syndrome, a case report shows.

Published in the journal Nephron, the case report of a 31-year-old woman diagnosed postpartum with autosomal recessive Alport syndrome (ARAS) highlights the importance of genetic testing to confirm the presence of the disease, investigators said. It also adds to the scant knowledge on potential pregnancy outcomes in this population.

The woman’s case was described by researchers from the Beth Israel Deaconess Medical Center in Boston in the study “Autosomal Recessive Alport Syndrome Unveiled by Pregnancy.”

ARAS accounts for only 15% of Alport syndrome cases. It is caused by genetic mutations affecting the collagen type 4 genes COL4A3 and COL4A4 — and not COL4A5, which is the most commonly affected gene in Alport syndrome.

COL4A5 is located on the X chromosome, making the disease more likely to manifest in males, since they only carry one X chromosome. In fact, Alport syndrome is not well-described in females  — who, in the majority of cases, are asymptomatic.

This report now described the case of a woman who started to have increased hematuria (red blood cells in urine) and proteinuria (increased levels of protein in urine) when she was 11-14 weeks pregnant.

Her urine protein levels kept rising during the pregnancy. By the third trimester, her blood creatinine levels — which are commonly used as a marker for poor kidney function — reached 1.9 mg/dL creatinine. The normal range is between 0.84 and 1.21 mg/dL. She reported no history of hematuria, proteinuria, or kidney disease before the pregnancy.

The birth was induced at 38 weeks gestation, and the woman gave birth to a healthy baby girl.

Seven weeks after delivery, her urine protein levels dropped. This improvement was accompanied by an increase in the blood albumin and a reduction of creatinine, suggesting a better renal function.

The clinical team decided to conduct additional assessments to better understand why she developed these renal symptoms.

The woman was negative for several autoimmune diseases and  for infection diseases like HIV or hepatitis. Next, physicians performed a kidney biopsy that showed the woman had scarring of the kidney’s filtering units, called glomeruli. She also had generalized thinning of the glomerular basement membrane with a few sites of thickening and splitting, which were suggestive of Alport syndrome.

After a genetic analysis, the team detected two new disease-causing genetic mutations in the COL4A4 gene, and she was diagnosed with ARAS.

The woman’s proteinuria levels remained high 10 months after giving birth. However, she did not show any additional hallmark features of the disease, such as vision or hearing problems, with the exception of mild myopia.

“Our case contributes to our knowledge [and] understanding of pregnancy outcomes in ARAS,” the researchers said. “It supports the current understanding that normal renal function, mild proteinuria, and lack of hypertension predict favorable pregnancy outcomes.”