Congenital renal diabetes insipidus caused by aquaporin 2 gene mutation in siblings: 2 cases report and literature review / 中国综合临床

Objective:To improve clinicians' understanding of congenital nephrogenital diabetes insipidus (CNDI) and to reduce missed and misdiagnosis. Methords 　Based on the literature, the clinical data and gene mutation of 2 patients with CNDI who were admitted to the Department of Endocrinology and Metabolism of the First Affiliated Hospital of Henan University of Science and Technology on July 30, 2020 were analyzed retrospectively. Results:(1) The presentee, 4 years old, had irritable thirst, polydipsia and polyuria for more than 3 years. The sister, 2.5 years old, had irritable thirst, polydipsia and polyuria for more than 2 years. The clinical diagnosis was “CNDI”, and the symptoms improved after treatment with hydrochlorothiazide. (2) The genetic test revealed that the congenital nephrogenic uremia and her sister had a heterozygous mutation of c.170A>C (p.Q57P) and c.211G>A (p.Vl71M) in the aquaporin-2 gene, and the mother carried the AQP2 gene. c.170A>C(p.Q57P) mutation.Conclusion:CNDI is a rare disease. Early diagnosis and treatment can improve the prognosis of patients to the greatest extent, and prenatal diagnosis can guide eugenics.

X-linked congenital renal diabetes insipidus caused by AVPR2 gene mutation: a case report / 天津医药

@#Objective A case of congenital renal diabetes insipidus caused by mutation of arginine vasopressin receptor 2 (AVPR2) gene was reported to explore the clinical significance of AVPR2 gene mutation in congenital nephrotic diabetes insipidus and improve the understanding of the disease. Methods The clinical data of proband and his parents were retrospectively analyzed, and the related literature was reviewed. All exons of AVPR2 were amplified by PCR, and the amplified products were purified and sequenced in two directions. Results The clinical manifestations of the children were recurrent fever and hypernatremia, and hyperchloremia was difficult to correct. There was no abnormality in pituitary nuclear magnetic resonance in the child at the beginning. Short T1 signal disappeared in the posterior pituitary lobe after reexamination. Central diabetes insipidus was not excluded from clinical practice. However, vasopressin test supported renal diabetes insipidus, which caused troubles in clinical diagnosis. The treatment of vasopressin acetate tablets was ineffective. The results of gene analysis confirmed that mutations were found in the subregion of AVPR2 gene in the proband: c.359T (thymine)>G (guanine) caused amino acid changes: p.Met120Arg, which was located on the X chromosome, and the mother of the patient was the carrier of the mutation of AVPR2 gene. Clinical application of hydrochlorothiazide and amiloride in the treatment of the child with urinary volume significantly reduced, confirmed as congenital renal diabetes insipidus. Conclusion Congenital renal diabetes insipidus in infants and young children is rare and its clinical manifestations are not specific. It can only be manifested by repeated fever and electrolyte disturbance, which causes troubles in clinical diagnosis. AVPR2 gene detection can be used for screening and gene diagnosis of congenital renal diabetes insipidus.

Nonobstructive Bilateral Hydronephrosis & Hydroureter from Nephrogenic Diabetes Insipidus with a Novel Mutation of AQP2 Gene (p.A123G)

Nephrogenic diabetes insipidus (NDI) can cause nonobstructive hydronephrosis. Congenital NDI (CNDI) is caused by a genetic mutation. This case report presents a 12-year-old girl who was incidentally diagnosed with nonobstructive hydronephrosis due to NDI caused by AQP2 gene mutation after being evaluated for microscopic hematuria found on routine health examination at school. The patient's medical and family history was unremarkable, and she complained of nocturia only at the time of the clinic visit. Bilateral hydronephrosis on abdominal ultrasonography prompted a water deprivation test, leading to diagnosis of NDI. Genetic study confirmed p.Asn (AAC)123Ser (AGC) in exon 2 of the AQP2 gene. Polyuria and hydronephrosis improved following arginine-vasopressin therapy. CNDI responsive to treatment should be considered as a possible cause of nonobstructive hydroureter.

Congenital Nephrogenic Diabetes Insipidus Presented with Bilateral Hydronephrosis: Genetic Analysis of V2R Gene Mutations

Most cases of hydronephrosis are caused by urinary tract obstruction. However, excessive polyuric syndrome rarely gives rise to non-obstructive hydronephrosis, megaureter, and a distended bladder. The authors report here on two cases of congenital nephrogenic diabetes insipidus (NDI) with severe bilateral hydronephrosis and megaureter. It is Interesting that the patients were symptomless except for their polyuria, and they both presented with bilateral hydronephrosis. Fluid deprivation testing revealed the presence of AVP resistant NDI. Gene analysis for these patients showed the AVP receptor 2 (V2R) missense mutations (Q225X and S126F), which have previously been reported on in other studies. We made the diagnosis of NDI by using a physiologic test, and we confirmed it by mutation analysis of the V2R gene.

A Case of Congenital Nephrogenic Diabetes Insipidus Presenting Fever in Neonatal Period / 대한주산의학회잡지

Congenital nephrogenic diabetes insipidus (NDI) is a rare disorder of the kidney characterized by the in ability to concentrate urine despite normal or elevated plasma concentration of the antidiuretic hormone agent vasopressin (AVP). We describe a case of congenital nephrogenic diabetes insipidus presenting with mild fever . The 3-day-old baby boy was admitted with mild fever. He has 6 members with DI in his family and his laboratoty finding showed hypernatremia, increased serum osmolarity and low level of urine specific gravity. Throughout the water deprivation test and the vasopressin test, he has been diagnosed as congenital NDI. Urinary free water loss was improved after treatment with hydrochlorothiazide and low salt formula. At the age 4 months, the infant has demonstrated normal growth and neurodevelopmental milestones. An early diagnosis of congenital NDI is very important, since the proper adequate management can prevent hyperosmolarity which might induce the delayed mental and physical development.

A Case of Autosomal Dominant Nephrogenic Diabetes Insipidus with Renal Failure / 대한신장학회잡지

Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited disorder. The X-linked recessive NDI, most of congenital DI (>90%), has been known to be caused by mutation of the AVPR2 gene. Less than 10% of congenital NDI has an autosomal recessive inheritance and mutations of the AQP2 gene. Although several adult cases of congenital NDI were reported in Korea, all of them had an X-linked recessive inheritance and no azotemia. We have experienced a case of autosomal dominant NDI with renal failure. A 38-year-old man was admitted due to polyuria and polydipsia. In his family, his grandfather, father, three sisters and nieces showed similar symptoms. On admission, serum creatinine level was 4.9 mg/dL and creatinine clearance decreased to 19.9 mL/min. On ultrasonography, both kidneys showed severe hydronephrosis. We performed water deprivation and vasopressin stimulation test, and the result was consistent with NDI. On gene mutational analysis of the two different genes, AVPR2 and AQP2, no specific mutations were found except polymorphism.

Congenital Nephrogenic Diabetes Insipidus Developing in the Mother and the Son / 대한신장학회잡지

Most cases of congenital nephrogenic diabetes insipidus (NDI) are transmitted in an X-linked recessive manner and are caused by mutations in the vasopressin type 2 receptor (AVPR2) genes on the long arm of the X chromosome (Xq28). In these cases, female carriers are usually asymptomatic, and most patients are male. X-linked NDI is a rare hereditary disease with an estimated prevalence and incidence of approximately four to nine per one million males. Although several cases of congenital NDI diagnosed in the childhood were reported in Korea, there were few reports about congenital NDI diagnosed in the adult and documented by the mutational analysis. We have experienced two cases of congenital NDI developing in the mother and the son, diagnosed in the adult, and confirmed to be caused by mutation (R113W) in AVPR2 gene. Therefore, we report these cases with a brief review of the literature.

A Case of Congenital Nephrogenic Diabetes Insipidus with Bilateral Hydronephrosis and Hydroureter / 대한신장학회잡지

We describe a case of congenital nephrogenic diabetes insipidus with severe dilatation of bilateral urinary tracts without anatomical obstructions. Functional obstruction can be occurred when polyuria surpasses the transporting ability of urine in the urinary tract. The patient was admitted to our hospital due to decreased mentality developed after traffic accident. On radiologic study, bilateral hydronephrosis and hydroureter were noted. Because the patient excreted copious dilute urine, we performed water deprivation test and the result was consistent with nephrogenic diabetes insipidus. We are presenting this case in an attempt to describe strong association between congenital diabetes insipidus and nonobstructive hydronephrosis in which polyuria is responsible for the hydronephrosis.

New Mutation Site in Vasopressin V2 Receptor Gene in a Family with Congenital Nephrogenic Diabetes Incipidus / 대한내분비학회지

BACKGROUND: Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited disorder, in which two different hereditary forms, X-linked and autosomal recessive traits, have been identified. The X-linked recessive form, mostly (>90%) congenital NDI, has been known to be caused by mutation of the arginine-vasopressin receptor 2 (AVPR2) gene. AVPR2 mutation sites are different in ethnic groups and recently 72 different mutation sites have been reported among AVPR2 gene. This study aimed to analyze AVPR2 gene in selected members in a Korean family with NDI and provided a report of the existence of a new mutation site in AVPR2 gene. METHODS: Three-generation maternal pedigree of the index patient (21-year old male, patient I) and his younger brother (19-year old male, patient II) with NDI was collected. Genomic DNA was obtained from patient I, II, III (index patient's male maternal cousin with NDI), index patient's mother, three maternal aunts, one female maternal cousin and, for control, one healthy male volunteer. Three coding exons of AVPR2 gene were amplified by PCR using 4 pairs of oligonucleotide primers. After direct sequencing of amplified PCR products, the sequence was compared with whole squence of normal AVPR2 gene and identification of a new site of mutation in this gene was done. RESULTS: 1) all three male patients had transversion of G to C at position 1033 of the AVPR2 gene, resulting in a subsequent change of amino acid from glycine to cysteine in codon 201. 2) Two small peaks of G and T, the result of direct sequencing in five female members in this family, would suggest that they are carriers of G to N transversion. CONCLUSION: These results can demonstrate the significant functional correlation of the mutation in AVPR2 gene sequence with clinical NDI, and suggest the clinical utility of direct mutation testing for congenital NDI in family.