Abstract: PUB176
Rare Case of X-Linked Hereditary Diabetes Insipidus
Session Information
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Vashisht, Archana, New York City Health and Hospitals Jacobi, New York, New York, United States
- Lu, Wenxia, New York City Health and Hospitals Jacobi, New York, New York, United States
- Petras, Fnu, New York City Health and Hospitals Jacobi, New York, New York, United States
- Rana, Bilal Azhar, New York City Health and Hospitals Jacobi, New York, New York, United States
- Acharya, Anjali, New York City Health and Hospitals Jacobi, New York, New York, United States
Group or Team Name
- Jacobi Fellows: Genetic Kidney Disease.
Introduction
Diabetes insipidus (DI) is a disorder characterized by the excretion of large volumes of dilute urine due to impaired renal water reabsorption. There are two major forms: Arginine Vasopressin deficiency DI and Arginine Vasopressin Resistance DI. X-linked nephrogenic diabetes insipidus (XL-NDI) is an uncommon hereditary form typically affecting males. Symptomatic female carriers are rare.
Case Description
45 year old woman with a pmh of uncontrolled T2DM, Obesity and persistent polyuria was being followed at Nephrology clinic for persistent polyuria. Initial evaluation attributed polyuria to osmotic diuresis from uncontrolled hyperglycemia with HbA1c levels between 9–13% and presence of glucosuria. Patient was evaluated by Nephrology once Hba1c was between 7.8 – 8.8. Serum glucose 150 – 200 mg/dl, S. K 5.1- 6.0 meq/L,S.Na 135-138mEq/L,S.BUN 19-29mg/dl,S.Cr 1.0 mg/dl. Urine studies enlisted in Table. Patient stated drinking ~ 5L of water a day. Estimated osmolar output was 660–1200 mosm/day. Pivotal point in case was patient’s revelation of a positive family history of DI in her son and grandson. Retrospective review showed symptoms of polyuria and polydipsia since childhood, worsening after her DM diagnosis. The patient experienced symptomatic relief with hydrochlorothiazide. Genetic testing revealed a heterozygous AVPR2 gene mutation: c.262G>A (p.Val88Met), pathogenic variant associated with XL-NDI. Patients symptoms spontaneously resolved.
Discussion
The AVPR2 gene encodes the arginine vasopressin receptor 2, mutations of which lead to renal insensitivity to vasopressin. The disorder primarily affects males due to its X-linked recessive inheritance, female carriers may exhibit variable phenotypic expression due to lyonization. This case illustrates a rare instance of symptomatic XL-NDI in a heterozygous female, highlighting the importance of family history and the utility of genetic testing. Presence of confounding comorbidities like DM may delay diagnosis.
Random Urine studies
| U. Osmolality (7/25/22) | 401 | mOsm/kg |
| U. Osmolality (8/1/22) | 308 | mOsm/kg |
| U. Osmolality (12/1/22) | 226 | mOsm/kg |
| U. Osmolality (3/15/23) | 373 | mOsm/kg |
| U. Osmolality (7/10/23) | 347 | mOsm/kg |
| UPCR | 190-260 | mg/gm |
| U. Urea | 479 | mg/dl |