Heterozygous X-linked Alport syndrome in a pregnant woman: A case report

Alport syndrome is a genetic disorder of chronic kidney disease, hearing loss, and ocular abnormalities, caused by mutations in type IV collagen. While X-linked Alport Syndrome demonstrates characteristic severe renal failure in males, it has a variable presentation in females. Here, we present a case of a pregnant woman who was found to have X-linked Alport Syndrome with a heterozygous c.3587G>A (p.Gly1196Glu) mutation in the COL4A5 gene. The patient presented in her third trimester of pregnancy with preexisting chronic proteinuria. Family history was notable for kidney failure in her mother and two brothers, consistent with suspected hereditary nephropathy. She developed worsening proteinuria and new-onset hematuria, without preeclampsia or renal failure, and was induced at 39 weeks with an uncomplicated delivery. Genetic testing revealed a heterozygous c.3587G>A (p.Gly1196Glu) mutation in the COL4A5 gene, consistent with X-linked Alport Syndrome. Postpartum, the patient had mildly worsened proteinuria that transiently reached nephrotic range before improving, with normal to low blood pressures. Out of concern for symptomatic hypotension, she was not a candidate for first-line therapy with renin-angiotensin-aldosterone system blockade. In cases of hereditary nephropathies such as X-linked Alport Syndrome, cascade testing may be highly considered to identify family members at risk. Our case demonstrates the variable phenotype of X-linked Alport Syndrome in females and the need for close management during pregnancy, along with the benefits of early genetic testing, given the risks of long-term renal, hearing, and ocular manifestations of this disease.