The underdiagnosed kidney burden of Fabry disease in females

Aim: Progressive kidney deterioration can occur in females with Fabry disease. Despite this, many females go undiagnosed or are labeled “carriers”. Our study aimed to review biopsy findings of adult female Fabry patients with creatinine values within the “normal reference ranges” and minimal proteinuria. Methods: This study was a single-center retrospective analysis of female patients presenting to the University of Alabama at Birmingham. Kidney biopsies and clinical characteristics were reviewed. Kidney biopsies were scored using the Fogo scoring system. Results: All of the 13 participants had classic mutations (11 nonsense, 2 missense). The mean age was 31.7 years. The median serum creatinine was 0.7 mg/dL (0.5-1.2), and estimated glomerular filtration rate (eGFR) values calculated using the chronic kidney disease epidemiology collaboration (CKD-EPI) equation ranged from 56 to 130 ml/min/1.73m2. The serologic biomarkers were not elevated in any of the patients - plasma Lyso globotriaosylsphingosine (Lyso GL-3) was < 5.1 ng/mL and globotriaosylceramide (GL-3) was < 3 µg/mL. The average score for the biopsies per the International Study Group of Fabry Nephropathy (ISGFN) was 2.43. Thirty-eight percent of patients had greater than 50% foot process effacement despite normal creatinine and minimal proteinuria. Conclusion: Females with Fabry disease, despite having normal reference range creatinine, minimal proteinuria, and low plasma Lyso GL-3, had significant histologic evidence of the disease. When possible, histologic assessment should be performed in females to assess tissue involvement. Longitudinal follow-up is needed to determine if histologic findings on presentation predict long-term outcomes.