Sporadic Case of Heterozygous X-Linked Alport Syndrome

Alport syndrome is a genetically and phenotypically heterogeneous disorder that can be transmitted in an X-linked, autosomal recessive, or autosomal dominant fashion and can affect glomerular, cochlear, and ocular basement membranes. The disorder results from mutations in the collagen IV genes COL4A5 (X chromosome), COL4A3, and COL4A4. Alport patients are at lifetime risk for kidney failure, sensorineural deafness, and ocular abnormalities. Males with Alport syndrome typically present with severe phenotype with progression to end-stage kidney disease and/or sensorineural deafness and eye changes. Females generally having less severe presentation and diagnosis of X-linked Alport syndrome are generally not considered. Here, we report a case of a 3-year-old girl with gross hematuria, proteinuria, and chronic kidney disease who was found to have features of Alport syndrome on kidney biopsy and a sporadic heterozygous pathogenic COL4A5 deletion on molecular testing. This case report emphasizes the importance of kidney biopsy and molecular testing in the work up of pediatric patients with hematuria, proteinuria, and/or chronic kidney disease. It is also a poignant illustration that females with heterozygous X-linked COL4A5 mutations are often affected patients. It further illustrates the phenomenon of sporadic occurrence of genetic kidney disease in the absence of family history of kidney disease.