Eujin Park1, Jiwon M Lee1,2, Yo Han Ahn1, Hee Gyung Kang1,3, I I Soo Ha1,4, Joo Hoon Lee5, Young Seo Park5, Nayoung K D Kim6, Woong-Yang Park7,8, Hae Ii Cheong9,10,11. 1. Department of Pediatrics, Seoul National University Children's Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 110-744, Korea. 2. Department of Pediatric Nephrology, Chungnam National University Children's Hospital, Daejeon, Korea. 3. Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea. 4. Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea. 5. Department of Pediatrics, Asan Medical Center, Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea. 6. Translational Bioinformatics Lab, Samsung Genome Institute, Samsung Medical Center, Seoul, Korea. 7. Samsung Genome Institute, Samsung Medical Center, Seoul, Korea. 8. Sungkyunkwan University School of Medicine, Seoul, Korea. 9. Department of Pediatrics, Seoul National University Children's Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 110-744, Korea. cheonghi@snu.ac.kr. 10. Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea. cheonghi@snu.ac.kr. 11. Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea. cheonghi@snu.ac.kr.
Abstract
BACKGROUND: Hepatorenal fibrocystic diseases (HRFCDs) are a group of monogenic disorders characterized by developmental abnormalities involving the liver and kidney. In this study, we performed genotype and phenotype analyses of children with HRFCDs to determine the distribution of underlying diseases. METHODS: A total of 36 children with HRFCDs were recruited, with genetic tests being performed in 22 patients and 14 patients diagnosed clinically as having autosomal recessive polycystic kidney disease (ARPKD). RESULTS: In children with HRFCDs, ARPKD was the most common disease, found in 16/36 (44.4 %), followed by nephronophthisis 13 (NPHP13) in 11/36 (30.6 %) and Meckel-Gruber syndrome type 3 (MKS3) in 4/36 (11.1 %). Renal function deteriorated faster in children with NPHP13. The main hepatic pathology was Caroli disease in the NPHP13 patients, while most other patients had Caroli syndrome or congenital hepatic fibrosis. Of note, three of four MKS3 patients had an accompanying choledochal cyst. No ARPKD patient had other organ involvement, while several NPHP13 patients had ocular and/or neurodevelopmental involvement. In contrast, all MKS3 patients had severe ocular and neurodevelopmental involvement. CONCLUSIONS: NPHP13 is a major disease in the HRFCD category, and thorough evaluation of its clinical features, including kidney, liver and other organ involvement, may aid in the differential diagnosis of HRFCD.
BACKGROUND:Hepatorenal fibrocystic diseases (HRFCDs) are a group of monogenic disorders characterized by developmental abnormalities involving the liver and kidney. In this study, we performed genotype and phenotype analyses of children with HRFCDs to determine the distribution of underlying diseases. METHODS: A total of 36 children with HRFCDs were recruited, with genetic tests being performed in 22 patients and 14 patients diagnosed clinically as having autosomal recessive polycystic kidney disease (ARPKD). RESULTS: In children with HRFCDs, ARPKD was the most common disease, found in 16/36 (44.4 %), followed by nephronophthisis 13 (NPHP13) in 11/36 (30.6 %) and Meckel-Gruber syndrome type 3 (MKS3) in 4/36 (11.1 %). Renal function deteriorated faster in children with NPHP13. The main hepatic pathology was Caroli disease in the NPHP13 patients, while most other patients had Caroli syndrome or congenital hepatic fibrosis. Of note, three of four MKS3patients had an accompanying choledochal cyst. No ARPKDpatient had other organ involvement, while several NPHP13 patients had ocular and/or neurodevelopmental involvement. In contrast, all MKS3patients had severe ocular and neurodevelopmental involvement. CONCLUSIONS: NPHP13 is a major disease in the HRFCD category, and thorough evaluation of its clinical features, including kidney, liver and other organ involvement, may aid in the differential diagnosis of HRFCD.
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