Abstract: TH-PO0614
ADCK4-Related Steroid-Resistant Nephrotic Syndrome with Intrafamilial Variability: A Case of Three Siblings
Session Information
- Monogenic Kidney Diseases: Glomerular
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Unes, Meghan Marie, Saint Louis University School of Medicine, St. Louis, Missouri, United States
- Barthel, Avrie, Saint Louis University School of Medicine, St. Louis, Missouri, United States
- Oto, Ozgur Akin, Istanbul Universitesi Dahili Tip Bilimleri, Istanbul, Turkey
- Dirim, Ahmet Burak, Istanbul Universitesi Dahili Tip Bilimleri, Istanbul, Turkey
- Caliskan, Yasar, SSM Health Saint Louis University Hospital, St. Louis, Missouri, United States
Introduction
Autosomal recessive ADCK4-related nephropathy is a cause of steroid-resistant nephrotic syndrome (SRNS) leading to focal segmental glomerulosclerosis (FSGS) and progressive kidney failure. We report a rare case of three siblings with ADCK4-related nephropathy, all harboring a homozygous ADCK4 pathogenic variant, with their parents confirmed heterozygous carriers.
Case Description
A non-consanguineous family with a history of kidney disease presented with three affected siblings. Sequencing revealed all three siblings carried a homozygous ADCK4 variant (NM_001142555: exon12: c.1076dupA: p.H359Qfs11 and NM_024876: exon13: c.1199dupA: p.H400Qfs11), resulting in a frameshift mutation and impaired Coenzyme Q10 (CoQ10) biosynthesis, causing mitochondrial dysfunction in podocytes.
Case 1 (Index): A female proband (red arrow in Figure 1) presented with nephrotic-range proteinuria (7g/day) at age 6. She was diagnosed with steroid-resistant FSGS at age 7 and progressed to ESKD, initiating dialysis the same year.
Case 2: A 14 year-old male presented with proteinuria (3.7g/day). He received a six-month oral steroid course for FSGS with no improvement and progressed to ESKD. Hemodialysis was initiated at age 15.
Case 3: A 24 year-old female presented with proteinuria (4.2g/day) and was diagnosed with FSGS. She received a preemptive kidney transplant from a living unrelated donor at age 26.
All three siblings progressed to ESKD at varying ages. Both parents were confirmed heterozygote carriers and showed no proteinuria, hematuria, or impaired renal function.
Discussion
This familial case of autosomal recessive ADCK4-related nephropathy emphasizes the importance of early genetic testing as this may have slowed disease progression through earlier detection and initiation of CoQ10 therapy. Intrafamilial variability in age of onset and disease severity underscore the complexity of genotype-phenotype correlations in ADCK4-related nephropathy.