ESPN 54th Annual Meeting

ESPN 2022


 
A rare cause of combined hepatic and renal failure: NPHP19 due to a novel DCDC2 variant in two siblings
GIZEM YILDIZ 1 MERAL TORUN BAYRAM 1 AHMET OKAY ÇAĞLAYAN 2 AYFER ÜLGENALP 2 ALPER SOYLU 1 SALIH KAVUKCU 1

1- DOKUZ EYLÜL UNIVERSITY MEDICAL FACULTY, DEPARTMENT OF PEDIATRIC NEPHROLOGY, IZMIR, TURKEY
2- DOKUZ EYLÜL UNIVERSITY MEDICAL FACULTY, DEPARTMENT OF PEDIATRIC GENETICS, IZMIR, TURKEY
 
Introduction:

Nephronophitisis-19 (NPHP19) is a rare autosomal recessive renal-hepatic ciliopathy due to variants in DCDC2 gene. This syndrome has only been reported in three patients previously. Hepatic involvement precedes renal involvement and is characterized by early onset hepatosplenomegaly, ductal plate malformation, hepatic fibrosis and cholestasis. Renal findings which may not be present at diagnosis include increased echogenicity, severe interstitial fibrosis, tubular dilatation with prominent epithelial luminal budding. We describe here two Turkish siblings with NPHP19 having previously undefined cardiac involvement.

Material and methods:

 Case Report

Results:

Two siblings presented due to chronic renal disease (CKD) and proteinuria at the ages of 7.5 (female) and 10 (male) years. Their parents were first degree relatives. Both had a history of liver transplantation at the ages of 2.5 and 1.5 years, respectively. They had neonatal cholestasis and liver pathology was characterized by biliary cirrhosis and hepatic fibrosis. Both had small echogenic kidneys and nephrotic range proteinuria. CKD stage was 3 and 2 in the girl and the boy, respectively. Kidney biopsy in the boy disclosed focal segmental glomerulosclerosis. Valvular aortic stenosis was detected in both siblings. End stage renal disease developed in the girl at 9 years of age and she died at 10-year of age due to sudden cardiac arrest. The boy is 13-year-old at present and still had stage 2 CKD and nephrotic range proteinuria. Genetic analysis for nephronophitisis panel revealed a novel likely pathogenic homozygous frameshift mutation in exon 7 of DCDC2 gene (chr6:24278358, c.840dup, p.Glu281ArgfdTer27) in both siblings.

Conclusions:

Renal involvement has been reported in two of three NPHP19 patients in the literature. We described two siblings with novel homozygous DCDC2 mutation who developed renal involvement during the first decade. ESRD developed at 9 years of age in one patient. In addition, both had cardiac involvement characterized by valvular aortic stenosis which has net been described previously.