Spectrum of clinical manifestations of X-linked Alport syndrome in girls: a single-center cohort study

Abstract

X-linked Alport syndrome (XLAS) is an inherited disorder caused by genetic variants in gene COL4A5. The frequency and the severity of clinical manifestations as well as the risk of glomerulopathy progression are variable in XLAS in females, and the disease course features have not been sufficiently studied as yet. Since patient management tactics is determined by the disease course nature, studying the spectrum of XLAS clinical manifestations and prognosis in girls remains relevant. The purpose of this research was to determine the spectrum and the features of clinical manifestations of XLAS in girls. Materials and methods used: a single-center cohort prospective study was carried out by the Authors that included 74 girls aged 2 to 17 y/o with genetically proven XLAS diagnosis. Authors have analyzed the patients’ medical records identifying sensorineural hearing loss (SNHL), arterial hypertension (AH; blood pressure (BP) over 95% than at the patient’s age/height), albuminuria (Alb; norm<30 mg/mmol of creatinine), proteinuria (Pr; norm<100 mg/sq m/day) - with its degree, decrease in estimated glomerular filtration rate (eGFR, ml/min/1.73 sq m; norm≥90 ml/min/1.73 sq m) and angiotensin-converting enzyme inhibitors (ACEIs) therapy data. Results: all patients had hematuria with episodical macrohematuria in 27% of cases, proteinuria in 40%, eGFR decrease in 15%, SNHL in 8% and peripheral retinopathy in 7%. Girls with missense v. those with non-missense variants of COL4A5 more often had macrohematuria (0.15 v. 0.05; p=0.015) and albuminuria (1 v. 0.5; p<0.001) whilst no statistically significant difference was showed in proteinuria frequency and age of onset (0.48 v. 0.5 and 6.5 [3; 11] v. 5 [5; 8] y/o), eGFR decrease (0.15 v. 0.15; 12.4±2.6 v. 13.2 ±2.8 y/o), SNHL (0.07 v. 0.1; 13±2.8 v. 14.4±3.1 y/o) and retinopathy (0.04 v. 0.15; 14.3±3.5 v. 12.6±2.9 y/o). ACEIs therapy did not show any statistically significant effect on the cumulative proportion of patients with both proteinuria and eGFR decrease (log-rank test=1.25, p=0.213 and log-rank test=0.66, p=0.512, respectively). Conclusion: the results obtained demonstrate the need for a dynamic follow-up of girls with XLAS with the purpose of earliest possible detection of proteinuria and timely prescribing with nephroprotective therapy as well as hearing loss diagnosing and timely audiological correction.