Rare Combination of Phenotypes of Karyomegalic Interstitial Nephritis and Autosomal Recessive Polycystic Kidney Disease in an Omani Child

Autosomal recessive polycystic kidney disease is one of the most prevalent inherited cystic kidney diseases in infants and children, common in highly consanguineous societies such as Oman. Karyomegalic interstitial nephritis is a rare cause of hereditary chronic kidney disease presenting with progre...

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Main Authors: Intisar Al Alawi, Maryam Al Shehhi, Naifain Al Kalbani, Aliya Al Hosni, Ashwaq Al Mimani, Issa Al Salmi, John A. Sayer
Format: Article
Language:English
Published: Oman Medical Specialty Board 2024-11-01
Series:Oman Medical Journal
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Online Access:https://omjournal.org/articleDetails.aspx?coType=1&aId=3868
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author Intisar Al Alawi
Maryam Al Shehhi
Naifain Al Kalbani
Aliya Al Hosni
Ashwaq Al Mimani
Issa Al Salmi
John A. Sayer
author_facet Intisar Al Alawi
Maryam Al Shehhi
Naifain Al Kalbani
Aliya Al Hosni
Ashwaq Al Mimani
Issa Al Salmi
John A. Sayer
author_sort Intisar Al Alawi
collection DOAJ
description Autosomal recessive polycystic kidney disease is one of the most prevalent inherited cystic kidney diseases in infants and children, common in highly consanguineous societies such as Oman. Karyomegalic interstitial nephritis is a rare cause of hereditary chronic kidney disease presenting with progressive renal impairment and hematoproteinuria. We report a rare case of concurrent karyomegalic interstitial nephritis and autosomal recessive polycystic kidney disease in a two-year-old Omani boy. He presented with failure to thrive, developmental delay, hypotonia, recurrent urinary tract infection, proteinuria, and hematuria. Abdominal ultrasonography showed bilaterally enlarged kidneys with distorted parenchyma, loss of corticomedullary differentiation, and multiple small cysts in addition to an enlarged liver. Whole exome sequencing of the patient DNA revealed a homozygous likely-pathogenic variant in FAN1(NM_014967.4:c.2854C>T, p.R952*) segregating from each parent, in addition to a homozygous missense variantin polycystic kidney and hepatic disease 1(NM_138694.3:c.406A>G, p.T136A). Familial carrier testing in parents and a similarly affected brother revealed segregation of thepolycystic kidney and hepatic disease 1 variant in a homozygous state in the father and brother, and in a heterozygous state in the mother. This case demonstrates two rare genetic causes of chronic kidney disease within a highly consanguineous family, mimicking an autosomal dominant pattern of inheritance of cystic kidney disease. We recommend whole exome sequencing as a routine molecular diagnostic tool for children with cystic kidney disease, especially those from consanguineous families.
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spelling doaj-art-57ccede4cb044c9089260695555bcc6f2025-08-20T02:09:42ZengOman Medical Specialty BoardOman Medical Journal1999-768X2070-52042024-11-01396e698e69810.5001/omj.2024.34Rare Combination of Phenotypes of Karyomegalic Interstitial Nephritis and Autosomal Recessive Polycystic Kidney Disease in an Omani ChildIntisar Al Alawi0Maryam Al Shehhi1Naifain Al Kalbani2 Aliya Al Hosni3Ashwaq Al Mimani4Issa Al Salmi5John A. Sayer6Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UKNational Genetic Centre, Royal Hospital, Muscat, OmanInternal Medicine Residency Training Program, Oman Medical Specialty Board, Muscat, OmanNational Genetic Centre, Royal Hospital, Muscat, OmanNational Genetic Centre, Royal Hospital, Muscat, OmanRenal Medicine Department, Royal Hospital, Muscat, OmanRenal Services, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UKAutosomal recessive polycystic kidney disease is one of the most prevalent inherited cystic kidney diseases in infants and children, common in highly consanguineous societies such as Oman. Karyomegalic interstitial nephritis is a rare cause of hereditary chronic kidney disease presenting with progressive renal impairment and hematoproteinuria. We report a rare case of concurrent karyomegalic interstitial nephritis and autosomal recessive polycystic kidney disease in a two-year-old Omani boy. He presented with failure to thrive, developmental delay, hypotonia, recurrent urinary tract infection, proteinuria, and hematuria. Abdominal ultrasonography showed bilaterally enlarged kidneys with distorted parenchyma, loss of corticomedullary differentiation, and multiple small cysts in addition to an enlarged liver. Whole exome sequencing of the patient DNA revealed a homozygous likely-pathogenic variant in FAN1(NM_014967.4:c.2854C>T, p.R952*) segregating from each parent, in addition to a homozygous missense variantin polycystic kidney and hepatic disease 1(NM_138694.3:c.406A>G, p.T136A). Familial carrier testing in parents and a similarly affected brother revealed segregation of thepolycystic kidney and hepatic disease 1 variant in a homozygous state in the father and brother, and in a heterozygous state in the mother. This case demonstrates two rare genetic causes of chronic kidney disease within a highly consanguineous family, mimicking an autosomal dominant pattern of inheritance of cystic kidney disease. We recommend whole exome sequencing as a routine molecular diagnostic tool for children with cystic kidney disease, especially those from consanguineous families.https://omjournal.org/articleDetails.aspx?coType=1&aId=3868autosomal recessive polycystic kidney diseasechronic kidney diseasewhole exome sequencingoman
spellingShingle Intisar Al Alawi
Maryam Al Shehhi
Naifain Al Kalbani
Aliya Al Hosni
Ashwaq Al Mimani
Issa Al Salmi
John A. Sayer
Rare Combination of Phenotypes of Karyomegalic Interstitial Nephritis and Autosomal Recessive Polycystic Kidney Disease in an Omani Child
Oman Medical Journal
autosomal recessive polycystic kidney disease
chronic kidney disease
whole exome sequencing
oman
title Rare Combination of Phenotypes of Karyomegalic Interstitial Nephritis and Autosomal Recessive Polycystic Kidney Disease in an Omani Child
title_full Rare Combination of Phenotypes of Karyomegalic Interstitial Nephritis and Autosomal Recessive Polycystic Kidney Disease in an Omani Child
title_fullStr Rare Combination of Phenotypes of Karyomegalic Interstitial Nephritis and Autosomal Recessive Polycystic Kidney Disease in an Omani Child
title_full_unstemmed Rare Combination of Phenotypes of Karyomegalic Interstitial Nephritis and Autosomal Recessive Polycystic Kidney Disease in an Omani Child
title_short Rare Combination of Phenotypes of Karyomegalic Interstitial Nephritis and Autosomal Recessive Polycystic Kidney Disease in an Omani Child
title_sort rare combination of phenotypes of karyomegalic interstitial nephritis and autosomal recessive polycystic kidney disease in an omani child
topic autosomal recessive polycystic kidney disease
chronic kidney disease
whole exome sequencing
oman
url https://omjournal.org/articleDetails.aspx?coType=1&aId=3868
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