Vasopressin function in familial cranial diabetes insipidus

Abstract

SummaryA family suffering from cranial diabetes insipidus, that extends over 4 generations, is described. Inheritance of polyuria was autosomal dominant. Vasopressin function was studied in members of the last 2 generations, 4 of whom had polyuria. Osmoregulation of vasopressin secretion was assessed by infusion of hypertonic saline. Plasma vasopressin remained undetectable in one patient, while 2 others had very blunted vasopressin responses to osmotic stimulation. Three non-osmotic stimuli were applied. Controlled hypotension produced by trimetaphan infusion and insulin-induced hypoglycaemia did not increase plasma vasopressin but apomorphine-induced nausea caused a minimal rise in plasma vasopressin to 0 7 pg/ml. Polyuria and thirst resolved with antidiuretic therapy in all patients studied.Congenital absence of vasopressin as in Brattleboro rats is unlikely to account for diabetes insipidus in this disorder since small increases in vasopressin have been demonstrated in these patients. In view of previous post-mortem findings, familial cranial diabetes insipidus is most likely to be due to degeneration of vasopressin-synthesizing neurones.

A single base substitution in the coding region for neurophysin II associated with familial central diabetes insipidus.

“…1). Accordingly, this pedigree was consistent with an autosomal dominant mode of inheritance which is usually observed in the reported pedigrees of FDI (1,2). Basal plasma AVP levels of the 2 patients studied were 0.26 and 0.36 pg/mi (III-I and 111-2, respectively).…”

“…According to the causes, CDI can be classified into three categories, familial, idiopathic, and secondary. Familial CDI (FDI) is an extremely rare disorder, usually transmitted as an autosomal dominant trait (1,2), while idiopathic CDI (IDI) is far more common, comprising -30% ofCDI (3).…”

A murine model of autosomal dominant neurohypophyseal diabetes insipidus reveals progressive loss of vasopressin-producing neurons

“…is an autosomal dominant disorder caused by a deficiency of the antidiuretic hormone arginine vasopressin (AVP) (1). Symptoms of diabetes insipidus, such as polyuria, polydipsia, and thirst, usually manifest several months or years after birth.…”

Possible involvement of inefficient cleavage of preprovasopressin by signal peptidase as a cause for familial central diabetes insipidus.

“…One of its categories, familial CDI, is usually transmitted as an autosomal dominant trait (4)(5)(6). We have previously reported a mutation in exon 2 of the VP gene in patients with familial CDI (6).…”