Case report confirms X-linked Alport syndrome diagnosis in a young girl with family history

BackgroundAlport syndrome (AS), one of the most common hereditary kidney diseases, is caused by mutations in genes encoding the α3–α5 chains of type IV collagen, and is characterized by persistent hematuria with or without proteinuria, sensorineural hearing loss, and ocular abnormalities. Progressive renal injury eventually leads to end-stage kidney disease (ESKD). Early interventions can dramatically delay the progression to ESKD. However, AS is often misdiagnosed, leading to mistreatments.Case presentationThe patient was a 4-year-2-month-old girl, who was incidentally noticed to have foamy morning urine, prompting admission to a local hospital. Repeated urinalyses detected persistent microscopic hematuria in 20 days. Then she was referred to our hospital. Given that her mother also had microscopic hematuria and her maternal grandmother had developed end-stage renal disease of unknown etiology, we excluded infection, autoimmune disorders, and other acquired causes of hematuria, and proceeded with renal biopsy and genetic testing. Electron microscopy showed focal thinning ( A, p.Gly545Ser) that was inherited from the mother. The same variant was subsequently detected in the affected maternal grandmother. This change is classified as likely pathogenic according to ACMG criteria. Currently, the patient is being treated with an angiotensin-converting enzyme inhibitor (ACEI).ConclusionEarly renal biopsy and comprehensive genetic analysis in a child with a positive family history of renal disease allowed the expedited diagnosis of X-linked Alport syndrome (XLAS), after the detection of persistent microscopic hematuria in 20 days. Our report highlights that females heterozygous for the COL4A5 (c.1633G > A, p.Gly545Ser) variant are not merely asymptomatic carriers but may develop renal failure, as illustrated by the disease progression in the maternal grandmother in this pedigree. The single gene COL4A5 variant, c.1633G > A, in AS patients has been previously reported, and its identification expands the mutational spectrum associated with XLAS and may facilitate future prenatal diagnosis and early therapeutic intervention.