Alport Disease in Young Females: Description, Clinical Presentation, and Disease Course

Inheritance of Alport disease, a multi-system disease, is most commonly linked to the X chromosome and has historically thought to be presymptomatic in young females. Previous studies and reports of outcomes have focused primarily on males and adult women. Selasie Goka, MD, and colleagues at Children’s Hospital of Philadelphia (CHOP), Pennsylvania, conducted a study designed to describe the clinical presentation and disease course of females with Alport disease in a large pediatric medical center.

Results of the study were reported during a poster session at Kidney Week 2019. The poster was titled Description of Alport Disease in Female Children and Adolescents. The single center retrospective review included pediatric female patients with Alport disease seen at CHOP between 1987 and 2018.

All female patients with International Classification of Diseases, Ninth and Tenth Editions codes for Alport, familial hematuria, and hereditary nephritis were identified. The bedside Chronic Kidney Disease in Children (CKiD) equation was used to calculate glomerular filtration rate (GFR). Hypertension was defined as systolic or diastolic blood pressure ≥95th percentile for age, gender, and height. Proteinuria was defined as ≥30 mg/dL of protein.

A total of 217 patients were identified. Of those, 164 were excluded due to an incorrect diagnosis, and 16 had missing charts. A total of 37 female patients were confirmed to have Alport disease and were included in the analysis.

Mean age at presentation was 5.4 years and mean follow-up was 6.3 years. Fourteen of the patients had genetic testing; of those, 80% demonstrated heterozygous mutations in the COL4A5 gene. Eleven patients had biopsies; the remaining patients were diagnosed based on clinical manifestation and family history.

At the end of follow-up, at least one episode of gross hematuria was seen in 15 patients, proteinuria was seen in 21 patients, and three patients had GFR <90 mL/min/1.73 m2. Seven patients had an abnormal audiogram. One patients required dialysis and received a deceased donor transplant.

“Most females diagnosed with Alport disease in childhood have persistent microscopic hematuria and normal renal function. Gross hematuria, proteinuria, and subclinical hearing involvement were common findings, suggesting that Alport disease should not be overlooked in girls with nephritis,” the researchers said.

Source: Goka S, Copelovitch LA, Levy Evez D. Description of Alport disease in female children and adolescents. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2019 (Abstract TH-PO1002), November 7, 2019, Washington, DC.