Nephrogenic diabetes insipidus associated with a new mutation in the AVPR2 gene

Diabetes insipidus (DI) is an orphan disease clinically characterized by profound thirst and the excretion of large volumes of dilute urine. Nephrogenic diabetes insipidus (NDI) is characterized by resistance to the action of antidiuretic hormone (ADH). Hereditary NDI is associated with mutations in the vasopressin receptor gene, AVPR2, in 90% of cases; less frequently, defects in the aquaporin-2 gene (AQP2) are observed. This clinical case presents a novel mutation in the AVPR2 gene (hemizygous mutation c.587T>C, p.Phe196Ser), which has not been previously documented in the literature, identified in a 29-year-old male. The patient reports significant thirst and polyuria since early childhood. The diagnosis of nephrogenic diabetes insipidus (NDI) was confirmed at three years of age against a backdrop of severe polyuria-polydipsia syndrome, aided by a water deprivation test. No increase in urine osmolality was observed following the administration of desmopressin. Magnetic resonance imaging (MRI) of the brain did not reveal any structural anomalies. Genetic analysis conducted at the age of 29 identified a rare mutation resulting in the substitution of phenylalanine (Phe) with serine (Ser) at position 196 of the receptor protein (p.Phe196Ser). The patient was advised to take a thiazide diuretic alongside potassium supplements, which led to a reduction in thirst and a decrease in urine output. However, after two weeks of treatment, symptomatic hypokalemia developed, necessitating the discontinuation of hydrochlorothiazide. Following this cessation, potassium levels stabilized, but NDI symptoms recurred. Therapy with non-steroidal anti-inflammatory drugs (NSAIDs) did not yield significant clinical effects. A decision was made to resume hydrochlorothiazide at a lower dose, in combination with potassium supplements and a potassium-sparing diuretic. The patient is under ongoing observation. This clinical case emphasizes the importance of an interdisciplinary approach in the differential diagnosis and treatment of diabetes insipidus, aimed at preventing complications and improving the quality of life for patients with polydipsia-polyuria syndrome.