Abstract: TH-PO328
Genotype, Phenotype, and Follow-Up in Taiwanese Patients with Congenital Nephrogenic Diabetes Insipidus
Session Information
- Sodium, Potassium, and Volume Disorders: Clinical
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Tseng, Min-hua, Chang Gung Memorial Hospital Linkou, Taoyuan, Taiwan
- Lin, Shih-Hua P., Tri-Service General Hospital, Taipei, Taiwan
Background
Genotype, phenotype, and follow-up outcome in Taiwanese patients with congenital nephrogenic diabetes insipidus (CNDI) due to arginine vasopressin V2 receptor (AVPR2) and the aquaporin 2 (AQP2) genetic mutations are not well evaluated. To investigate the phenotypic, genetic characteristics, and outcomes in the Taiwanese families with CNDI.
Methods
Twenty-seven patients (M:F=21:6, age 22 ± 17) with CNDI belonging to eighteen unrelated Taiwanese families were enrolled. Genomic DNA from blood leukocytes was analyzed for AVPR2 and AQP2 genes mutations. deamino D-arginine vasopressin (dDAVP) stimulation was administered to separate these two gene mutations. Clinical symptoms and biochemical studies at the first presentation as well as follow-up were examined.
Results
Of the 27 patients with CNDI, 17 have AVPR2 mutations and 10 have AQP2 mutations. Eleven mutations, including 6 missense, 3 novel small deletion, and 2 large deletion mutation, and four mutations, including Q57P, G100V, 592InsC, and R253Dfs*82 were identified in AVPR2 and AQP2 gene, respectively. Q57P and G100V of AQP2 were recurrent, and Q57P exerted a founder effect. All patients developed phenotypic polyuria and polydipsia. All patients with AVPR2 mutations lack of normal hypotensive and coagulation responses to dDAVP. One symptomatic female patient with heterozygous V115X mutation in AVPR2 gene had inactivated X chromosome in another allele. Three patients who carried same mutation (F178Q) from one family have different phenotypic severity. Seven patients have non-obstructive hydroureteronephrosis. Seven patients, 4 AVPR2 and 3 AQP2 mutations, reached chronic kidney disease (CKD, stage III-V) during the follow-up.
Conclusion
Q57P in AQP2 is the Taiwanese founder mutation. Non-obstructive hydroureteronephrosis is not uncommon complication. Chronic kidney disease should be aware in congenital NDI cases caused by either AVPR2 or AQP2 mutations.
Funding
- Government Support – Non-U.S.