Endocrine Abstracts

Introduction: Familial neurohypophyseal diabetes insipidus (FNDI) is a rare form of central diabetes insipidus (CDI) characterized by childhood-onset progressive polydipsia and polyuria due to mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene.

Case description: Two male siblings were referred at 1 month of age to exclude CDI owing to a family history of CDI in the father and paternal grandfather. The proband was the father diagnosed at 3 months old. The grandparent was diagnosed later, in his early twenties, when diuresis was about 15 L daily. His symptoms had apparently not been recognised since childhood. At 6 months of age, the older sibling (1) drank 500 ml of water/night and 1.5 L of water/daily and the younger sibling (2), at 11 months old, drank 800 ml of water/night and had 2 diaper changes/night, in a total of 2500 ml water intake and 8 diaper changes/day. No growth deceleration was observed in both. Physical examination and past medical history were unremarkable. Random urine specific gravity was lower than 1.005. Glycemia, thyroid function, serum osmolality, 8 am. cortisol, creatinine, sodium, potassium and calcium were within normal range. The sibling 1 was admitted for elective water deprivation test that confirmed CDI (basal serum and urinary osmolality: 278 mOsm/Kg and 292 mOsm/kg; serum and urinary osmolality at the end: 289 mOsm/kg and 281 mOsm/kg; urinary osmolality after 10 mg of desmopressin [DDAVP]: urinary osmolality of 574 mOsm/kg [increased by 102%]). He promptly initiated DDAVP (0.025 mg, twice daily) with clinical improvement. Pituitary magnetic resonance imaging confirmed a small and hypointense neurohypophysis. CDI was presumptively assumed in the sibling 2, and symptoms improved under DDAVP (0.025 mg, twice daily). Sequencing analysis of the AVP-NPII gene revealed the same mutation in the four family members, a heterozygous nonsense mutation in the NPII coding region (c.343G>T, p.Glu115Ter) of the AVP-NPII gene. Currently, the four patients are asymptomatic under DDAVP.

Discussion and conclusions: To our knowledge, there is only another family with this autosomal dominant mutation described worldwide. Genetic counselling should be offered to ensure an early and adequate diagnosis and treatment. It should also provide the family with accurate information on preimplantation genetic testing (PGT) in order to obtain genetically healthy descendants. In Portugal, FNDI requires prior authorization from the “National Council for Medically Assisted Procreation” for couples who intend to perform a PGT cycle.