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Levtchenko E, Ariceta G, Arguedas Flores O, Bichet DG, Bockenhauer D, Emma F, Hoorn EJ, Koster-Kamphuis L, Nijenhuis T, Trepiccione F, Vargas-Poussou R, Walsh SB, Knoers NVAM. International expert consensus statement on the diagnosis and management of congenital nephrogenic diabetes insipidus (arginine vasopressin resistance). Nat Rev Nephrol 2025; 21:83-96. [PMID: 39438674 DOI: 10.1038/s41581-024-00897-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/13/2024] [Indexed: 10/25/2024]
Abstract
Congenital nephrogenic diabetes insipidus (NDI; also known as arginine vasopressin resistance) is a rare inherited disorder of water homeostasis, caused by insensitivity of the distal nephron to arginine vasopressin. Consequently, the kidney loses its ability to concentrate urine, which leads to polyuria, polydipsia and the risk of hypertonic dehydration. The diagnosis and management of NDI are very challenging and require an integrated, multidisciplinary approach. Here, we present 36 recommendations for diagnosis, treatment and follow-up in both children and adults, as well as emergency management, genetic counselling and family planning, for patients with NDI. These recommendations were formulated and graded by an international group of experts in NDI from paediatric and adult nephrology, urology and clinical genetics from the European Rare Kidney Disease Reference Network and the European Society of Paediatric Nephrology, as well as patient advocates, and were validated by a voting panel in a Delphi process. The goal of these recommendations is to provide guidance to health care professionals who care for patients with NDI and to patients and their families. In addition, we emphasize the need for further research on different aspects of this potentially life-threatening disorder to support the development of evidence-based guidelines in the future.
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Affiliation(s)
- Elena Levtchenko
- Department of Paediatric Nephrology, Emma Children's Hospital, Amsterdam University Medical Centre, Amsterdam, The Netherlands.
| | - Gema Ariceta
- Department of Paediatric Nephrology, Hospital Vall d' Hebron, Autonomous University of Barcelona, Barcelona, Spain
| | - Olga Arguedas Flores
- Department of Paediatric Urology, Emma Children's Hospital, Amsterdam University Medical Centre, Amsterdam, The Netherlands
| | - Daniel G Bichet
- Nephrology Service, Hôpital du Sacré-Coeur de Montréal, Departments of Medicine, Pharmacology and Physiology, University of Montreal, Québec, Canada
| | - Detlef Bockenhauer
- Paediatric Nephrology, University Hospital and Catholic University Leuven, Leuven, Belgium
- Great Ormond Street Hospital for Children NHS Foundation Trust and Department of Renal Medicine, University College London, London, UK
| | - Francesco Emma
- Division of Nephrology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Ewout J Hoorn
- Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Linda Koster-Kamphuis
- Department of Paediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Tom Nijenhuis
- Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Francesco Trepiccione
- Department of Medical Translational Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
- Biogem Institute of Molecular Biology and Genetics, Ariano Irpino, Italy
| | - Rosa Vargas-Poussou
- Department of Genomic Medicine for Rare Diseases, Reference Centre for Hereditary Kidney Diseases of Children and Adults MARHEA, Assistance Publique Hôpitaux de Paris - Hôpital Européen Georges Pompidou, Paris, France
| | - Stephen B Walsh
- London Tubular Centre, Department of Renal Medicine, Department of Renal Medicine, University College London, London, UK
| | - Nine V A M Knoers
- Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
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Ghasemi S, Mojbafan M, Talebi S, Hooman N, Hoseini R. Genetic analysis of nephrogenic diabetes insipidus patients: A study on the Iranian population. Mol Genet Genomic Med 2024; 12:e2421. [PMID: 38622833 PMCID: PMC11019120 DOI: 10.1002/mgg3.2421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Revised: 02/19/2024] [Accepted: 03/19/2024] [Indexed: 04/17/2024] Open
Abstract
INTRODUCTION Nephrogenic diabetes insipidus (NDI) is a rare genetic disease that causes water imbalance. The kidneys play a crucial role in regulating body fluids by controlling water balance through urine excretion. This highlights their essential function in managing the body's water levels, but individuals with NDI may have excess urine production (polyuria), that leads to excessive thirst (polydipsia). Untreated affected individuals may exhibit poor feeding and failure to thrive. This disease is caused by mutations in the AVPR2 and the AQP2 genes which have the X-linked and autosomal recessive/dominant inheritance, respectively. Both of these genes are expressed in the kidney. METHODS Twelve Iranian patients from 10 consanguineous families were studied in this project. DNA was extracted from the whole blood samples of the patients and their parents. All coding exons and exon-intron boundaries of the AVPR2 and AQP2 genes were sequenced in the affected individuals, and the identified variants were investigated in the parents. All variants were analyzed according to the ACMG (American College of Medical Genetics and Genomics) guidelines. RESULTS In this study, 6 different mutations were identified in the patients, including 5 in the AQP2 gene (c.439G>A, c.538G>A, c.140C>T, c.450T>A, and the novel c.668T>C) and 1 in the AVPR2 gene (c.337C>T) in the present study. DISCUSSION As expected, all the detected mutations in this study were missense. According to the ACMG guideline, the identified mutations were categorized as pathogenic or likely pathogenic. Unlike previous studies which showed more than 90% of mutations were in the AVPR2 gene, and only less than 10% of the mutations were in the AQP2 gene, it was found that more than 90% of our identified mutations located in the AQP2 gene, and only one mutation was observed in the AVPR2 gene, which seems it may be a result of the high rate of consanguineous marriages in the Iranian population. We observed genotype-phenotype correlation in some of our affected individuals, and some of the mutations were observed in unrelated families from same ethnicity which could be suggestive of a founder mutation.
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Affiliation(s)
- Saeed Ghasemi
- Department of Medical GeneticsSchool of Medicine, Iran University of Medical Sciences (IUMS)TehranIran
| | - Marzieh Mojbafan
- Department of Medical GeneticsSchool of Medicine, Iran University of Medical Sciences (IUMS)TehranIran
- Department of Medical GeneticsAli‐Asghar Children's HospitalTehranIran
| | - Saeed Talebi
- Department of Medical GeneticsSchool of Medicine, Iran University of Medical Sciences (IUMS)TehranIran
- Department of Medical GeneticsAli‐Asghar Children's HospitalTehranIran
| | - Nakysa Hooman
- Department of Pediatric NephrologyAli‐Asghar Children's HospitalTehranIran
- Clinical Research Development CenterIran University of Medical SciencesTehranIran
| | - Rozita Hoseini
- Department of Pediatric NephrologyAli‐Asghar Children's HospitalTehranIran
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Yang LL, Xu Y, Qiu JL, Zhao QY, Li MM, Shi H. Congenital nephrogenic diabetes insipidus arginine vasopressin receptor 2 gene mutation at new site: A case report. World J Clin Cases 2022; 10:13443-13450. [PMID: 36683631 PMCID: PMC9850987 DOI: 10.12998/wjcc.v10.i36.13443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 11/11/2022] [Accepted: 12/08/2022] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary disorder. It is associated with mutations in the arginine vasopressin receptor 2 (AVPR2) gene and aquaporin 2 (AQP2) gene, and approximately 270 different mutation sites have been reported for AVPR2. Therefore, new mutations and new manifestations are crucial to complement the clinical deficiencies in the diagnosis of this disease. We report a case of a novel AVPR2 gene mutation locus and a new clinical mani-festation.
CASE SUMMARY We describe the case of a 48-d-old boy who presented with recurrent fever and diarrhea 5 d after birth. Laboratory tests showed electrolyte disturbances and low urine specific gravity, and imaging tests showed no abnormalities. Genetic testing revealed a novel X-linked recessive missense mutation, c.283 (exon 2) C>T (p.P95S). This mutation results in the substitution of a proline residue with a serine residue in the AVPR2 protein sequence. The diagnosis of CNDI was confirmed based on the AVPR2 gene mutation. The treatment strategy for this patient was divided into two stages, including physical cooling supplemented with appropriate amounts of water in the early stage and oral hydrochlorothia-zide (1-2 mg/kg) after a clear diagnosis. After follow-up of one and a half years, the patient gradually improved.
CONCLUSION AVPR2 gene mutations in new loci and new clinical symptoms help clinicians understand this disease and shorten the diagnosis cycle.
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Affiliation(s)
- Lu-Lu Yang
- Department of Pediatrics, Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
| | - Yan Xu
- Department of Pediatrics, Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
| | - Jian-Li Qiu
- Department of Pediatrics, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
| | - Qian-Yi Zhao
- Department of Pediatrics, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
| | - Man-Man Li
- Department of Pediatrics, Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
| | - Hui Shi
- Department of Pediatrics, Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
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Ishida A, Mizuno H, Aoyama K, Sasaki S, Negishi Y, Arakawa T, Mori T. Partial nephrogenic diabetes insipidus with a novel arginine vasopressin receptor 2 gene variant. Clin Pediatr Endocrinol 2022; 31:44-49. [PMID: 35002068 PMCID: PMC8713061 DOI: 10.1297/cpe.2021-0029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 08/19/2021] [Indexed: 11/04/2022] Open
Abstract
X-linked nephrogenic diabetes insipidus (NDI) is caused by variations in arginine vasopressin receptor 2 (AVPR2). Some patients show partial resistance to arginine vasopressin (AVP). A 19-month-old Japanese boy presented with polydipsia since infancy. His mother had a history of polydipsia during pregnancy, and his maternal granduncle also had polydipsia. Intermediate urine osmolality and markedly high plasma AVP levels were observed in the water deprivation test. Subsequent pitressin administration caused no further elevation in urine osmolality. We diagnosed the patient with partial NDI, initiated therapy with hydrochlorothiazide, and placed him on a low-sodium diet. Although his urine volume decreased by 20-30% after the initiation of therapy, progressive hydronephrosis and growth retardation developed 2 years later. We investigated his genetic background by multiplex targeted sequencing of genes associated with inherited renal diseases, including AVPR2 and aquaporin-2 (AQP2). We identified a hemizygous missense variant in AVPR2 NM_000054:c.371A>G,p.(Tyr124Cys) in the boy and a heterozygous variant in the mother at the same locus. Distinguishing partial NDI from primary polydipsia is difficult because of its mild symptoms. Markedly elevated plasma AVP levels with intermediate urine osmolality may suggest partial NDI, and genetic analysis can be useful for such patients.
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Affiliation(s)
- Atsushi Ishida
- Department of Pediatrics, Gifu Prefectural Tajimi Hospital, Tajimi, Japan
| | - Haruo Mizuno
- Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan
| | - Kohei Aoyama
- Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Shiori Sasaki
- Department of Pediatrics, Gifu Prefectural Tajimi Hospital, Tajimi, Japan.,Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Yutaka Negishi
- Department of Pediatrics, Gifu Prefectural Tajimi Hospital, Tajimi, Japan.,Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Takeshi Arakawa
- Department of Pediatrics, Gifu Prefectural Tajimi Hospital, Tajimi, Japan
| | - Takayasu Mori
- Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
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Liao P, Xiang T, Li H, Fang Y, Fang X, Zhang Z, Cao Q, Zhai Y, Chen J, Xu L, Liu J, Tang X, Liu X, Wang X, Luan J, Shen Q, Chen L, Jiang X, Ma D, Xu H, Rao J. Integrating Population Variants and Protein Structural Analysis to Improve Clinical Genetic Diagnosis and Treatment in Nephrogenic Diabetes Insipidus. Front Pediatr 2021; 9:566524. [PMID: 33996673 PMCID: PMC8116627 DOI: 10.3389/fped.2021.566524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 03/05/2021] [Indexed: 11/13/2022] Open
Abstract
Congenital nephrogenic diabetes insipidus (NDI) is a rare genetic disorder characterized by renal inability to concentrate urine. We utilized a multicenter strategy to investigate the genotype and phenotype in a cohort of Chinese children clinically diagnosed with NDI from 2014 to 2019. Ten boys from nine families were identified with mutations in AVPR2 or AQP2 along with dehydration, polyuria-polydipsia, and severe hypernatremia. Genetic screening confirmed the diagnosis of seven additional relatives with partial or subclinical NDI. Protein structural analysis revealed a notable clustering of diagnostic mutations in the transmembrane region of AVPR2 and an enrichment of diagnostic mutations in the C-terminal region of AQP2. The pathogenic variants are significantly more likely to be located inside the domain compared with population variants. Through the structural analysis and in silico prediction, the eight mutations identified in this study were presumed to be disease-causing. The most common treatments were thiazide diuretics and non-steroidal anti-inflammatory drugs (NSAIDs). Emergency treatment for hypernatremia dehydration in neonates should not use isotonic saline as a rehydration fluid. Genetic analysis presumably confirmed the diagnosis of NDI in each patient in our study. We outlined methods for the early identification of NDI through phenotype and genotype, and outlined optimized treatment strategies.
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Affiliation(s)
- Panli Liao
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Tongji Medical College, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Tianchao Xiang
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Hongxia Li
- Tongji Medical College, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Ye Fang
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Xiaoyan Fang
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Zhiqing Zhang
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Qi Cao
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Yihui Zhai
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Jing Chen
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Linan Xu
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Jialu Liu
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Xiaoshan Tang
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Xiaorong Liu
- Department of Nephrology, Beijing Children's Hospital Affiliated to Capital University of Medical Science, Beijing, China
| | - Xiaowen Wang
- Tongji Medical College, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Jiangwei Luan
- Tongji Medical College, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Qian Shen
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Lizhi Chen
- Department of Pediatric, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaoyun Jiang
- Department of Pediatric, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Duan Ma
- Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Hong Xu
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Jia Rao
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
- State Key Laboratory of Medical Neurobiology, School of Basic Medical Science, Institute of Brain Science, Fudan University, Shanghai, China
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Chen MC, Hsiao YC, Chang CC, Pan SF, Peng CW, Li YT, Liu CD, Liou JW, Hsu HJ. Valine-279 Deletion-Mutation on Arginine Vasopressin Receptor 2 Causes Obstruction in G-Protein Binding Site: A Clinical Nephrogenic Diabetes Insipidus Case and Its Sub-Molecular Pathogenic Analysis. Biomedicines 2021; 9:301. [PMID: 33804115 PMCID: PMC8002004 DOI: 10.3390/biomedicines9030301] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 03/11/2021] [Accepted: 03/12/2021] [Indexed: 11/17/2022] Open
Abstract
Congenital nephrogenic diabetes insipidus (CNDI) is a genetic disorder caused by mutations in arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 genes, rendering collecting duct cells insensitive to the peptide hormone arginine vasopressin stimulation for water reabsorption. This study reports a first identified AVPR2 mutation in Taiwan and demonstrates our effort to understand the pathogenesis caused by applying computational structural analysis tools. The CNDI condition of an 8-month-old male patient was confirmed according to symptoms, family history, and DNA sequence analysis. The patient was identified to have a valine 279 deletion-mutation in the AVPR2 gene. Cellular experiments using mutant protein transfected cells revealed that mutated AVPR2 is expressed successfully in cells and localized on cell surfaces. We further analyzed the pathogenesis of the mutation at sub-molecular levels via long-term molecular dynamics (MD) simulations and structural analysis. The MD simulations showed while the structure of the extracellular ligand-binding domain remains unchanged, the mutation alters the direction of dynamic motion of AVPR2 transmembrane helix 6 toward the center of the G-protein binding site, obstructing the binding of G-protein, thus likely disabling downstream signaling. This study demonstrated that the computational approaches can be powerful tools for obtaining valuable information on the pathogenesis induced by mutations in G-protein-coupled receptors. These methods can also be helpful in providing clues on potential therapeutic strategies for CNDI.
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Affiliation(s)
- Ming-Chun Chen
- Department of Pediatrics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan; (M.-C.C.); (Y.-C.H.)
- Department of Pediatrics, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan
| | - Yu-Chao Hsiao
- Department of Pediatrics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan; (M.-C.C.); (Y.-C.H.)
| | - Chun-Chun Chang
- Department of Laboratory Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan;
- Department of Laboratory Medicine and Biotechnology, College of Medicine, Tzu Chi University, Hualien 97004, Taiwan
| | - Sheng-Feng Pan
- Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan; (S.-F.P.); (Y.-T.L.)
| | - Chih-Wen Peng
- Department of Life Science, College of Science and Engineering, National Dong Hwa University, Hualien 974301, Taiwan; (C.-W.P.); (C.-D.L.)
| | - Ya-Tzu Li
- Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan; (S.-F.P.); (Y.-T.L.)
| | - Cheng-Der Liu
- Department of Life Science, College of Science and Engineering, National Dong Hwa University, Hualien 974301, Taiwan; (C.-W.P.); (C.-D.L.)
| | - Je-Wen Liou
- Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan; (S.-F.P.); (Y.-T.L.)
| | - Hao-Jen Hsu
- Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan; (S.-F.P.); (Y.-T.L.)
- Department of Life Sciences, College of Medicine, Tzu Chi University, Hualien 97004, Taiwan
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Huang L, Ma L, Li L, Luo J, Sun T. Case Report: A Case of Congenital Nephrogenic Diabetes Insipidus Caused by Thr273Met Mutation in Arginine Vasopressin Receptor 2. Front Pediatr 2021; 9:707452. [PMID: 34336746 PMCID: PMC8319565 DOI: 10.3389/fped.2021.707452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 06/17/2021] [Indexed: 11/13/2022] Open
Abstract
Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary tubular dysfunction caused mainly by X-linked recessive inheritance of AVPR2 gene mutations. Pathogenic genes are a result of mutations in AVPR2 on chromosome Xq28 and in AQP2 on chromosome 12q13. The clinical manifestations of CNDI include polyuria, compensatory polydipsia, thirst, irritability, constipation, developmental delay, mental retardation, persistent decrease in the specific gravity of urine, dehydration, and electrolyte disorders (hypernatremia and hyperchloremia). Herein, we report a rare case of CNDI caused by an AVPR2 mutation in a 2-year-old Chinese boy who had sustained polyuria, polydipsia, and irritability for more than 20 months. Laboratory examinations showed no obvious abnormality in blood sodium and chloride levels but decreased urine osmolality and specific gravity. Imaging findings were also normal. However, genetic analysis revealed a C > T transition leading to T273M missense mutations in AVPR2. We provided the boy a low-sodium diet and administered oral hydrochlorothiazide and indomethacin for 1 month, after which his clinical symptoms significantly improved. This case report suggests that CNDI is characterized by pathogenic T273M missense mutations alone and expands our understanding of the pathogenesis of CNDI.
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Affiliation(s)
- Li Huang
- Department of Pediatric Nephrology, Lanzhou University Second Hospital, Lanzhou, China.,Department of Nephrology, Gansu Children's Hospital, Lanzhou, China
| | - Lina Ma
- Department of Pediatric Nephrology, Lanzhou University Second Hospital, Lanzhou, China.,Department of Nephrology, Gansu Children's Hospital, Lanzhou, China
| | - Linjing Li
- Department of Pediatric Nephrology, Lanzhou University Second Hospital, Lanzhou, China.,Department of Nephrology, Gansu Children's Hospital, Lanzhou, China
| | - Jiajia Luo
- Department of Pediatric Nephrology, Lanzhou University Second Hospital, Lanzhou, China.,Department of Nephrology, Gansu Children's Hospital, Lanzhou, China
| | - Tianhong Sun
- Department of Pediatric Nephrology, Lanzhou University Second Hospital, Lanzhou, China.,Department of Nephrology, Gansu Children's Hospital, Lanzhou, China
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8
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Lin FT, Li J, Xu BL, Yang XX, Wang F. Congenital nephrogenic diabetes insipidus due to the mutation in AVPR2 (c.541C>T) in a neonate: A case report. World J Clin Cases 2020; 8:6418-6424. [PMID: 33392325 PMCID: PMC7760441 DOI: 10.12998/wjcc.v8.i24.6418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 10/06/2020] [Accepted: 10/26/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary renal disorder that is caused by mutations in AVPR2 or aquaporin 2 (AQP2). Up to now, there are few reports about CNDI in neonates. Early clinical manifestations of CNDI in neonates are atypical. A lack of understanding of the disease by clinicians causes frequent misdiagnoses or missed diagnoses, which may result in failure to administer treatments in time and ultimately leads to severe complications. In this study, clinical data of a case of AVPR2 gene mutation-induced CNDI, which was confirmed by genetic testing, were retrospectively analyzed to improve our understanding of this disease.
CASE SUMMARY On February 1, 2020, a male neonate was hospitalized 17 d after birth due to a 7 d period of pyrexia. The patient’s symptoms included recurrent pyrexia, hypernatremia and hyperchloremia, which were difficult to treat. The patient was fed on demand, and water was additionally provided between milk intakes. A combination treatment of hydrochlorothiazide and amiloride was administered. After the treatment, body temperature and electrolyte levels returned to normal, the volume of urine was significantly reduced and the patient was subsequently discharged. Genetic tests confirmed that the patient carried the AVPR2 gene missense mutation c.541C>T (P.R181C), and the patient’s mother carried a heterozygous mutation at the same locus. After clinical treatment with a combination of hydrochlorothiazide and amiloride, the body temperature and electrolyte levels returned to normal. Up until the most recent follow-up examination, normal body temperature, electrolyte levels and growth and development were observed.
CONCLUSION CNDI in the neonatal period is rare, and its clinical manifestations are unspecific with some patients merely showing recurrent fever and electrolyte disturbance. Genetic testing of AVPR2 and AQP2 can be used for screening and genetic diagnosis of CNDI.
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Affiliation(s)
- Fa-Tao Lin
- Department of Neonatology, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou 450000, Henan Province, China
| | - Jing Li
- Department of Neonatology, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou 450000, Henan Province, China
| | - Bang-Li Xu
- Department of Neonatology, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou 450000, Henan Province, China
| | - Xiu-Xiu Yang
- Department of Neonatology, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou 450000, Henan Province, China
| | - Fang Wang
- Department of Infectious Diseases, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou 450000, Henan Province, China
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Liu JS, Huang H, Jin JY, Du R, Wang CY, Fan LL. Identification of a Novel Arginine Vasopressin Receptor 2 Mutation (p.V183M) in a Chinese Family with Nephrogenic Diabetes Insipidus. Mol Syndromol 2020; 11:130-134. [PMID: 32903920 DOI: 10.1159/000507035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/28/2020] [Indexed: 11/19/2022] Open
Abstract
Loss of function of arginine vasopressin receptor 2 (AVPR2) may affect the recognition and binding of arginine vasopressin (AVP) which, in turn, may prevent the activation of Gs/adenylate cyclase and reduce the reabsorption of water by renal tubules and combined tubes. Finally, the organism may suffer from nephrogenic diabetes insipidus (NDI), a kind of kidney disorder featured by polyuria and polydipsia, due to a break of water homeostasis. In this study, we enrolled a Chinese family with polyuria and polydipsia. The proband presented abnormal fluid intake and excessive urine output. A water deprivation and AVP stimulation test further indicated that this patient had NDI. By sequencing known causative genes for diabetes insipidus, we identified a novel mutation in AVPR2 (c.547G>A; p.V183M) in the family. This mutation, located in a conserved site of AVPR2 and predicted to be disease-causing by informatics programs, was absent in our 200 controls and other public databases. Our study not only further confirms the clinical diagnosis, but also expands the spectrum of AVPR2 mutations and contributes to genetic diagnosis and counseling of patients with NDI.
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Affiliation(s)
- Ji-Shi Liu
- Department of Nephrology, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Hao Huang
- Department of Cell Biology, The School of Life Sciences, Central South University, Changsha, China
| | - Jie-Yuan Jin
- Department of Cell Biology, The School of Life Sciences, Central South University, Changsha, China
| | - Ran Du
- Department of Cell Biology, The School of Life Sciences, Central South University, Changsha, China
| | - Chen-Yu Wang
- Department of Cell Biology, The School of Life Sciences, Central South University, Changsha, China
| | - Liang-Liang Fan
- Department of Nephrology, The Third Xiangya Hospital of Central South University, Changsha, China.,Department of Cell Biology, The School of Life Sciences, Central South University, Changsha, China
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Ding C, Beetz R, Rittner G, Bartsch O. A female with X‐linked Nephrogenic diabetes insipidus in a family with inherited central diabetes Insipidus: Case report and review of the literature. Am J Med Genet A 2020; 182:1032-1040. [DOI: 10.1002/ajmg.a.61516] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 01/16/2020] [Accepted: 01/28/2020] [Indexed: 12/17/2022]
Affiliation(s)
- Can Ding
- Institute of Human GeneticsUniversity Medical Centre of the Johannes Gutenberg University Mainz Germany
| | - Rolf Beetz
- Pediatric Nephrology Unit of the Children's HospitalUniversity Medical Centre of the Johannes Gutenberg University Mainz Germany
| | - Gabriele Rittner
- Institute of Human GeneticsUniversity Medical Centre of the Johannes Gutenberg University Mainz Germany
| | - Oliver Bartsch
- Institute of Human GeneticsUniversity Medical Centre of the Johannes Gutenberg University Mainz Germany
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