Heterozygous X-Linked Alport Syndrome in a Pregnant Woman: A Case Report

Introduction: Alport Syndrome is a genetic disorder presenting with renal failure, hearing loss, and ocular abnormalities. It is caused by mutations in the genes coding for Type IV collagen, which constitute the basement membrane of the glomerulus, cochlea, and ocular structures. Alport Syndrome can be inherited in an X-linked, autosomal recessive, or autosomal dominant fashion. While X-linked Alport Syndrome (XLAS) demonstrates characteristic severe renal failure in males, it has variable presentation in females given spontaneous X-linked inactivation. Here, we present a case of a pregnant female individual with chronic proteinuria who was found to have XLAS with a heterozygous c.3587G>A (p.Gly1196Glu) mutation in the COL4A5 gene. Case Description: A female patient in her third trimester of pregnancy presented with chronic proteinuria and a significant family history for renal pathologies. Over the remainder of her pregnancy, she developed worsening proteinuria and new onset hematuria, but without progression to preeclampsia or renal failure. She was induced at 39 weeks with an uncomplicated delivery. Genetic testing revealed a heterozygous c.3587G>A (p.Gly1196Glu) mutation in the COL4A5 gene, causing XLAS. Over 4 months in the postpartum period, the patient demonstrated mildly worsened subnephrotic proteinuria with low-to-normal blood pressure. She did not have any hearing or vision changes. No treatment was appropriate at this time given the patient’s stable blood pressure and renal status. Discussion: Our case demonstrates the variable phenotype of XLAS in females and the need for careful management during pregnancy. Given the significant renal manifestations possible with XLAS in female individuals, it is imperative to further explore its effects on maternal and fetal outcomes in pregnancy and options for long-term management.Figure 1. Renal function over time. UPCR: urine protein to creatinine ratio. BUN: blood urea nitrogen. UACR: urine microalbumin to creatinine ratio.