ESPN 53rd Annual Meeting

ESPN 2021


 
PHENOTYPE-GENOTYPE CORRELATION AND CLINICAL CHARACTERISTICS OF PEDIATRIC PATIENTS WITH ALPORT SYNDROME
MICHAŁ PAC 1 ŁUKASZ OBRYCKI 1 PAULINA HALAT-WOLSKA 2 ELŻBIETA CIARA 2 JANUSZ FEBER 3 MIECZYSŁAW LITWIN 1

1- DEPARTMENT OF NEPHROLOGY, KIDNEY TRANSPLANTATION AND HYPERTENSION, CHILDREN`S MEMORIAL HEALTH INSTITUTE, WARSAW, POLAND
2- DEPARTMENT OF MEDICAL GENETICS, THE CHILDREN’S MEMORIAL HEALTH INSTITUTE, WARSAW, POLAND
3- DIVISION OF NEPHROLOGY, DEPARTMENT OF PEDIATRICS, THE CHILDREN’S HOSPITAL OF EASTERN ONTARIO, OTTAWA
 
Introduction:

We aimed to analyse the correlation between clinical characteristics of Alport syndrome patients and their genotype.

Material and methods:

Next-generation sequencing was performed in 84 patients (40 girls, 48%; mean age 12.3±5.5 years) referred to the Department of Nephrology, Kidney Transplantation and Hypertension in Children`s Memorial Health Institute in Warsaw with suspected Alport syndrome. We determined the presence of pathogenic COL4A3, COL4A4 and COL4A5 variants and compared it with the clinical manifestations of the disease including renal function, proteinuria, hematuria, arterial hypertension, ocular abnormalities and hearing defects.

Results:

Pathogenic variants were found in total of 68 patients (81%), COL4A3 in 7 patients (8%), COL4A4 in 13 patients (15%), COL4A5 in 48 patients (57%), including the most common variant p.Gly624Asp in 13 patients (15%), 2 patients (2%) had co-existing COL4A3 and COL4A5 common variant. Fourteen patients (17%) had no mutation identified.  Statistically significant differences in microalbuminuria (p=0.020) and protein excretion (p=0.048) between the genotypes were found. Patients with non-p.Gly624Asp-COL4A5 mutation were younger at hematuria detection (p=0.034), had higher microalbuminuria (p=0.008) and protein excretion (p=0.013) and more often presented ocular symptoms (p=0.009). The predictors of GFR reduction for all patients were: older age of diagnosis (p=0.005), hypertension (p=0.007) and hypertension coexisting with proteinuria above 500 mg/24h (p=0.007); and for non-p.Gly624Asp-COL4A5 patients:  male gender (p=0.035), ocular symptoms (p=0.007) and microalbuminuria (p=0.054).

Conclusions:

Patients with non-p.Gly624Asp-COL4A5 mutation had the most severe clinical manifestation with male gender, ocular symptoms and microalbuminuria as predictors of lower GFR.

 

Partially supported: CMHI-M29/18