Alport Syndrome in a Woman with Proteinuria and Familial Hematuria

Introduction: Approximately 80% of Alport cases are due to X-linked gene mutations in COL4A5, although homozygous variants exist in people with autosomal recessive disease. The best screening tool for Alport syndrome is urinalysis with evidence of hematuria1. The diagnosis should be considered in patients with persistent microscopic hematuria or gross hematuria, although definitive diagnosis is by genetic testing3. Case Description: A 27-year-old female with a history of major depressive disorder presented to the clinic as a referral due to profound proteinuria on screening urinalysis by OBGYN for first trimester screening. Family history revealed persistent hematuria in the patient, her mother and brother. Autoimmune workup including Lupus was unremarkable with negative ANA. No signs of systemic inflammation were present, and inflammatory markers were within normal limits. We decided to perform genetic testing with NATERA Renasight Kidney Gene panels to determine if there is any hereditary explanation for her hematuria, ultimately avoiding a very high-risk kidney biopsy procedure during pregnancy. Her genetic testing came back positive c.2452G>A (p.Gly818Arg) mutation for COL43A gene. We have decided that Alport syndrome is the most likely explanation for her benign hematuria. We plan to obtain kidney biopsy following the delivery of her baby for confirmation of the diagnosis. However, with family history of multiple family members, genetic testing showing mutation the mutation above, and negative extensive work up, her most likely diagnosis is currently Alport Syndrome. Discussion: algorithm for diagnosing CKD. Genetic testing is emerging as a valuable component for the evaluation of CKD cause. The prevalence of genetic causes of CKD is expected to increase in future years as our screening methods and diagnostic tools become more available and cost effective3. In our case, it helped prevent possible complications that can arise with kidney biopsy during pregnancy, and gave us more information for reproductive counseling. We believe that genetic testing should be considered as an initial diagnostic tool in CKD diagnosis.