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Objective: Diabetes insipidus (DI) can be classified into 2 types: central/neurogenic DI and nephrogenic DI. Most cases of central DI occur after brain surgery, trauma, tumor, or infection. Here we report a rare case of familial central DI due to a heterozygous AVP gene mutation. Methods: A case of familial neurogenic DI has been described with thorough clinical, laboratory, and genetic workup. PubMed and Google scholar databases were used for literature discussion. Results: A 22-year-old man presented with polyuria and polydipsia. He drank about 4 gallons of water everyday and urinated large volumes very frequently. His physical examination was unremarkable. After 2 hours of water-deprivation, his serum sodium level was 147 mmol/L, serum osmolality was 302 mOsm/kg with concurrent urine osmolality of 78 mOsm/kg, vasopressin level was

A 17 9/12-year-old female with familial diabetes insipidus (FDI) and idiopathic hypoparathyroidism is described. We analyzed the arginine vasopressin-neurophysin II (AVP-NPII) gene in her family, and a novel heterozygous mutation in exon 2 of the AVP-NPII gene was noted in the patient and her mother. This deletion mutation results in a frame shift beginning at codon 70 and a premature termination at codon 80. Only two cases of non-FDI and idiopathic hypoparathyroidism have been reported so far, but there has been no report on the association of FDI and idiopathic hypoparathyroidism. The causes of this association are not known and it is not known whether it is accidental or not.

Familial hypothalamic diabetes insipidus is an autosomal dominant disorder characterized by deficient vasopressin synthesis. Different point mutations in the vasopressin-neurophysin (VP-NP) precursor gene have been found in affected families. In a Dutch kindred, a single G to T transversion in the NP-encoding exon B of one allele converts the highly conserved glycine 17 to a valine residue. In order to examine whether this point mutation affects the processing and transport of the VP-NP precursor, the normal (HV2) and mutant (MT6) vasopressin cDNAs were stably expressed in the mouse pituitary cell line AtT20. The normal precursor was correctly glycosylated and processed, and NP was detected in the culture medium. Secretion of NP was stimulated by 8-bromo-cAMP, indicating that the normal precursor was targeted to the regulated secretory pathway. In contrast, the mutant precursor was synthesized, but processing and secretion were dramatically reduced. The mutant precursor was core-glycosylated but remained endoglycosidase H-sensitive, suggesting that the protein did not reach the trans-Golgi network. These results were supported by immunocytochemical studies. In HV2 cells, NP derived from the precursor was concentrated in the tips of the cell processes where secretory granules accumulate. In MT6 cells, NP staining was restricted to the endoplasmic reticulum (ER) as determined by colocalization with an ER-resident protein, BiP. These results suggest that the mutation within the conserved part of NP alters the conformation of the precursor and thus triggers its retention in the ER.

Es wird uber eine Sippe berichtet, in der unter 28 Mitgliedern in 4 Generationen bei 12 Patienten ein Diabetes insipidus neurohormonalis vorlag. Der Erbgang des Leidens war einfach dominant mit wechselnder Expressivitat. In Zusammenhang mit den beschriebenen Beobachtungen wird auf das Vorkommen von Abortivformen der Erkrankung und auf die Schwierigkeiten der Diagnose des Diabetes insipidus hyperchloraemicus occultus im Sauglingsalter hingewiesen. Die bei unseren Beobachtungen auffallend haufige Kombination von Diabetes insipidus und Adipositas wird erwahnt.

Four cases of nephrogenic familial diabetes insipidus in two different families are described. The youngest of these cases (a boy of 5 1/2 months) exhibited considerable disturbances of water and electrolyte metabolism, whilst his mother showed only mild manifestations of the disease. In both patients the serum adiuretin level (toad test) was normal, but there was no response to adiuretin in the infant and reduced sensitivity of the tubule in the mother. The infant gradually developed a feeling of thirst after prolonged infusion therapy with hypotonic solutions to counteract hyperosmolarity. — In the second family two brothers (2 and 5 years old) likewise had the disease in varying degrees of severity as indicated by the clinical manifestations and the adiuretin test. The pathogenesis of this recessive and sex-linked disorder is discussed.

Rats with familial diabetes insipidus (D.I.) were exposed to liquids in which the solute was either excreted (NaCl), metabolized (glucose), or partially excreted-metabolized (milk). In the presence of an isosmotic solution where all the solvent was utilized for clearance of the solute (NaCl), rats continued to drink but displayed aphagia; decrease in the osmolality of NaCl solutions resulted in a proportional recovery of solid food ingestion. Exposure to milk resulted in hypophagia. Glucose solution did not interfere with the maintenance of eating, however, rats with D.I. did not increase their intake of glucose solution during solid food deprivation. Experimental evidence supports the view that the state of hydration as indicated by the body-fluid osmolality is essential for the maintenance of solid food ingestion. The evidence for a primary caloric regulation was doubtful.

Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare autosomal dominant disorder characterized by polyuria and polydipsia due to deficiency of arginine vasopressin (AVP). More than 50 mutations causing adFNDI have been already reported in the AVP gene. The aim of the present study is to analyze the AVP gene in four generations of one Brazilian kindred with adFNDI. The proband was a 31-year old female with huge hypotonic polyuria (10 L/day) dated from childhood. Molecular analysis included amplification of all exons and exon-intron regions of the AVP gene by PCR and direct sequencing. Sequencing analysis showed a novel point mutation in heterozygous: G88V (GGC>GTC). All affected patients presented the same mutation also in heterozygous, while it was absent in four normal members. We expand the repertoire of mutations in AVP describing the novel G88V mutation in one Brazilian kindred with adFNDI. Diabetes insípido neuro-hipofisário com herança autossômica dominante (adFNDI) é uma doença autossômica dominante rara, caracterizada por poliúria e polidipsia devido à deficiência de arginina-vasopressina (AVP). Mais de 50 mutações causando adFNDI foram descritas no gene AVP. O objetivo deste estudo foi analisar o gene AVP em quatro gerações de uma família brasileira com DINF. O caso-índice é de uma paciente de 31 anos, com volumosa poliúria hipotônica desde a infância (10 L/dia). A análise molecular incluiu amplificação por PCR e seqüenciamento automático dos éxons e regiões éxon-íntron do gene AVP. A análise do seqüenciamento mostrou uma nova mutação de ponto em heterozigose: G88V (GGC>GTC). Todos os pacientes afetados apresentaram a mesma mutação, que não foi encontrada em quatro indivíduos normais da família. Expandimos a lista de mutações no gene AVP, descrevendo a nova mutação G88V em uma família brasileira com adFNDI.

Familial diabetes insipidus is a rare occurrence. Paschkis, Rakoff, and Cantarow in their recent book "Clinical Endocrinology" state that 1 out of 70 cases was studied at the Peter Bent Brigham Hospital and none of 42 cases was studied at the University of Michigan. According to those authors: "The most impressive family tree contains 45 cases among 220 members of a family, in 5 generations. The transmission is probably through a dominant gene." Gates cites Weil's classic case reported in 1884, in which there were 23 affected (14 male and 9 female) in four generations. "The original progenitor was born in 1772 in Oberhessen [Germany] and had 220 descendants in five generations, 34 of whom had diabetes insipidus. Weil Jr. (1908) added 11 cases in the fifth generation of this family, making 34 cases (22 male-12 female) in five generations, the sibships numbering 34 affected: 46 normal. This is an