Phenotype, genotype, and clinical outcome of Taiwanese with congenital nephrotic syndrome

Min-Hua Tseng; Shih-Hua Lin; Wen-Lang Fan; Ta-Wei Wu; Shuan-Pei Lin; Jhao-Jhuang Ding; I-Jung Tsai; Jeng-Daw Tsai

doi:10.1016/j.jfma.2023.10.003

Phenotype, genotype, and clinical outcome of Taiwanese with congenital nephrotic syndrome

J Formos Med Assoc. 2023 Oct 14:S0929-6646(23)00404-7. doi: 10.1016/j.jfma.2023.10.003. Online ahead of print.

Authors

Min-Hua Tseng¹, Shih-Hua Lin², Wen-Lang Fan³, Ta-Wei Wu⁴, Shuan-Pei Lin⁵, Jhao-Jhuang Ding⁶, I-Jung Tsai⁷, Jeng-Daw Tsai⁸

Affiliations

¹ Division of Nephrology, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
² Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
³ Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
⁴ Fetal and Neonatal Institute, Division of Neonatology, Children's Hospital Los Angeles, CA, USA; Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
⁵ Division of Pediatric Genetics, Department of Pediatrics, MacKay Children's Hospital, Taipei, Taiwan.
⁶ Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
⁷ Division of Nephrology, Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan. Electronic address: ijtsai@ntu.edu.tw.
⁸ Division of Nephrology, Department of Pediatrics, MacKay Children's Hospital, Taipei, Taiwan; Department of Medicine, MacKay Medical College, New Taipei City, Taiwan; Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan; Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: tsaijd@yahoo.com.tw.

PMID: 37845138
DOI: 10.1016/j.jfma.2023.10.003

Abstract

Background/purpose: Congenital nephrotic syndrome (CNS) is one of the important causes of end-stage kidney disease in children. Studies on the genotype, phenotype, and clinical outcome in infants with CNS caused by genetic mutations are scarce.

Methods: We analyzed the genetic background, clinical manifestations, treatment response, and prognosis of pediatric patients with CNS in Taiwan.

Results: Fifteen infants with CNS were enrolled, and 11 patients of median age 21 (interquartile range 3∼44) days caused by genetic mutations from 10 unrelated families were included in the study. Of the eleven patients, 9 had extra-renal manifestations including microcephaly, facial dysmorphism, and skeletal anomalies. More than two-thirds of the patients had disease onset before 1 month of age. Diffuse meningeal sclerosis was the most common histological characteristic. Whole exome sequencing followed by direct Sanger sequence revealed mutations in OSGEP (R247Q), WT1 (R366H and R467Q), LAMB2 (Q1209∗ and c. 5432-5451 19 bp deletion), NUP93 (D302V), and LAGE3 (c.188+1G > A). Three of the variants were novel. Corticosteroids and/or immunosuppressants were administered in 2 patients, but both were refractory to treatment. During the mean 3.5 years of follow-up, all but two died of uremia and sepsis. The two survivors reached end-stage kidney disease and required peritoneal dialysis, and one of them underwent uneventful renal transplantation.

Conclusions: The majority of patients with CNS in Taiwan were caused by OSGEP followed by WT1 mutation. R247Q is the hotspot mutation of OSGEP in Taiwan. CNS patients in Taiwan suffer from significant morbidity and mortality.

Keywords: Congenital; Genetic association studies; Health care; Nephrosis; Outcome assessment.