Abstract
Congenital Nephrogenic Diabetes Insipidus with First Presentation as an Adult: A Case Report
Background:
Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited condition, usually presenting during the first year of life. It is characterized by a renal insensitivity to arginine vasopressin. About 90% of patients are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. Females are typically asymptomatic. Here, we report female case of NDI initially presenting and diagnosed in an adult woman.
Clinical Case:
A previously well 47-year-old woman of Italian descent underwent an elective laparoscopic repair of an abdominal hernia. Her medical history included obesity and migraine headaches. She was not taking any medications prior to admission. She had a bowel perforation 6 days after surgery, necessitating an emergency right hemicolectomy and small bowel resection. Upon instituting bowel rest with nil per os (NPO), she developed severe hypernatremia (Na+ 163 mmol/L) with polyuria (>6 L/day) and dilute urine (osmolality 174 mmol/kg). Further inquiry revealed that the patient routinely drank at least 10 L/day of fluids throughout her entire adult life. Her family history was remarkable for polydipsia affecting at least additional six people across three generations (including her son, her mother, 3 maternal uncles and 1 nephew). Following administration of desmopressin 1 ug subcutaneously, her urine remained inappropriately dilute (osmolality 160 mmol/kg) with no significant change in urine output (rate 350 mL/h for 3 hours). Her arginine vasopressin level was detectable (3.2 pmol/L, reference range 0.8–3.5 pmol/L), consistent with nephrogenic diabetes insipidus. Subsequent molecular analysis of the AVPR2 gene, located on chromosome Xq28, confirmed a pathogenic mutation (c.253G>A), consistent with a p.Asp85Asn substitution resulting in decreased binding affinity between the V2 receptor and arginine vasopressin. Thus, X-linked NDI was diagnosed according to the patient’s presentation, compatible family history, and genetic analysis. When she was able to eat and drink ad lib again, a low-salt, low-protein diet along with a trial of a thiazide diuretic were recommended. The patient remained well with 3 years of follow-up.
Conclusion:
The diagnosis of congenital NDI may be delayed until adulthood because of a relatively mild phenotype and compensatory drinking behavior, so that the disorder will not be clinically apparent until a person is deprived of free water. Men and women alike can be affected by this X-linked dominant condition which should be considered in any polyuric, hypernatremic hospitalized patient.
Severe congenital nephrogenic diabetes insipidus in a compound heterozygote with a new large deletion of the
AQP2
gene. A case report
