ESPN 53rd Annual Meeting

ESPN 2021

Larisa Prikhodina 1 Svetlana Papizh 1 Olga Katysheva 1

1- Veltishev Research & Clinical Institute of Pediatrics, Moscow, Russia


Introduction. Schimke immunoosseous dysplasia (SIOD; OMIM #242900) is an autosomal recessive multisystem disorder characterized by spondyloepiphyseal dysplasia, T-cell deficiency, and nephrotic syndrome (NS) progressing to ESKD during childhood. The aim of the study was to investigate clinical and molecular characteristics in Russian children with SIOD.

Methods. Retrospective analysis of phenotype and genotype of 10 children (6M/4F) with SIOD was conducted. Kidney biopsy performed in two subjects revealed FSGS. The median follow-up period was 14.5 (IQR: 11.8; 24.5) months. SMARCAL1 mutations were identified by direct Sanger sequencing (n=5) and NGS (n=5).

Results. Low birth weight (LBW) resulted from intrauterine growth restriction (IUGR) had 10/10 (100%) children with SIOD.  The median age at onset of NS was 49.0 (IQR: 38.0; 51.0) months. Among patients with SIOD NS, spondyloepiphyseal dysplasia and T-cell deficiency had 10/10 (100%) children, cerebral ischemic events had 5/10 (50%), hematological abnormalities and CAKUT had 4/10 (40%), respectively. Pathogenic homozygous (n=5) or compound heterozygous (n=4) nonsense variant с.2542G>T (p.Glu848*) in the SMARCAL1 gene was identified in 9/10 (90%) of individuals. One child had compound heterozygous SMARCAL1 variant c.994delA (p.R332fs); c.2070+2dupT. The median age of genetic diagnosis of SIOD was 54.0 (IQR: 44.0; 58.0) months. At the last follow-up of patients aged 5.5 (IQR: 4.5; 6.4) years progression to CKD was found in all children, including stage 2 CKD in 4/10 (40%) subjects, stage 3 CKD in 2/10 (20%), stage 4 CKD in 1/10 (10%) and ESKD in 3 (30%) individuals.

Conclusion. We conclude that Russian children with SIOD characterized by LBW due to IUGR, NS, spondyloepiphyseal dysplasia, immunodeficiency, and common SMARCAL1 pathogenic variant с.2542G>T (p.Glu848*).