A Novel Form of Familial Vasopressin Deficient Diabetes Insipidus Transmitted in an X-linked Recessive Manner.

Context: Familial pituitary diabetes insipidus has been described only in an autosomal dominant or recessive mode of inheritance.

Objective: This work aims to determine the cause of a novel form of familial diabetes insipidus (DI) that is controlled by desmopressin therapy but segregates in an X-linked recessive manner.

Methods: Thirteen members from 3 generations of the kindred with familial DI were studied.

Differential diagnosis of familial diabetes insipidus.

Diabetes insipidus (DI) is a syndrome characterized by the persistent excretion of abnormally large volumes of dilute urine. It can be caused by any of four fundamentally different abnormalities: deficient production of the antidiuretic hormone, arginine vasopressin (AVP) by magnocellular neurons that form the posterior pituitary (hypothalamic DI); impaired renal effects of AVP (nephrogenic DI); reduced AVP secretion due to excessive water intake (primary polydipsia); or degradation of AVP by placental vasopressinase (gestational DI). Each type of DI can be caused or potentiated by other disorders.

Hypernatremic Hydrophobic Transient Adipsia Without Organic or Severe Psychiatric Disorder.

Context: Psychogenic adipsic hypernatremia is an exceedingly rare and life-threatening condition, occurring in those with severe psychiatric disorders. Its diagnosis requires exclusion of congenital or acquired hypothalamic pathologic entities. We present the case of a patient who experienced transient severe hypernatremia without evidence of brain pathologic features or known psychiatric disease.

The effects of mutating Tyr9 and Arg15 on the structure, stability, conformational dynamics and mechanism of GSTA3-3.

Glutathione S-transferase A3-3 is the most catalytically efficient steroid isomerase enzyme known in humans, transforming Δ-androstene-3-17-dione into Δ-androstene-3-17-dione. GSTA3-3 catalyzes this reaction with ten-fold greater efficiency than GSTA1-1, its closest competitor in the Alpha class of GSTs. In order to examine the differences between Alpha class GSTs and to better elucidate the mechanism of GSTA3-3 the roles of Tyr9 and Arg15 were examined.

Diabetes insipidus: Differential diagnosis and management.

Diabetes insipidus (DI) is a syndrome characterized by the excretion of abnormally large volumes of dilute urine. It can be caused by any of 4 fundamentally different defects that must be distinguished for safe and effective management. They are: (1) pituitary DI, due to inadequate production and secretion of antidiuretic hormone, arginine-vasopressin (AVP); (2) gestational DI due to degradation of AVP by an enzyme made in placenta; (3) primary polydipsia, due to suppression of AVP secretion by excessive fluid intake; and (4) nephrogenic DI due to renal insensitivity to the antidiuretic effect of AVP.

Clinical review: Treatment of neurohypophyseal diabetes insipidus.

Context: In recent years, there have been several improvements in the treatment of neurohypophyseal diabetes insipidus (DI). They include new formulations of the vasopressin analog, desmopressin; a better understanding of the effect of fluid intake on dosing; and more information about treatments of infants, children, and pregnant women who present special challenges. This review aims to summarize past and current information relative to the safety and efficacy of treatments for the types of DI caused by a primary deficiency of vasopressin.

Temporal delays and individual variation in antidiuretic response to desmopressin.

This study aimed to estimate the relationship between pharmacokinetics and the antidiuretic effect of desmopressin. In the investigator-blind, randomized, parallel group study, 5 dose groups and 1 placebo group, each consisting of 12 healthy, overhydrated, nonsmoking male subjects 18-55 yr of age were infused intravenously over 2 h with placebo or 30, 60, 125, 250, and 500 ng desmopressin in 50 ml of normal saline. Plasma desmopressin and urine osmolality rose by variable amounts during the infusions of 60, 125, 250, and 500 ng desmopressin.

Familial forms of diabetes insipidus: clinical and molecular characteristics.

Over the past two decades, the genetic and molecular basis of familial forms of diabetes insipidus has been elucidated. Diabetes insipidus is a clinical syndrome characterized by the excretion of abnormally large volumes of diluted urine (polyuria) and increased fluid intake (polydipsia). The most common type of diabetes insipidus is caused by lack of the antidiuretic hormone arginine vasopressin (vasopressin), which is produced in the hypothalamus and secreted by the neurohypophysis.

Vaptans for the treatment of hyponatremia.

The vaptans constitute a new class of pharmaceuticals developed for the treatment of the hypervolemic and euvolemic forms of hyponatremia. These agents are nonpeptide vasopressin antagonists that interfere with the antidiuretic effect of the hormone by competitively binding to V(2) receptors in the kidney. This blockade results in water diuresis (aquaresis) that, if not offset by increased fluid intake, reduces body water content and raises plasma sodium levels.

Semivolatile organic compounds in residential air along the Arizona-Mexico border.

Concerns about indoor air quality and the potential effects on people living in these environments are increasing as more reports about the toxicities and the potential indoor air exposure levels of household-use chemicals and chemicals from housing and fumishing manufacture in air are being assessed. Gas chromatography/mass spectromery was used to confirm numerous airborne contaminants obtained from the analysis of semipermeable membrane devices deployed inside of 52 homes situated along the border between Arizona and Mexico. We also describe nontarget analytes in the organochlorine pesticide fractions of 12 of these homes; this fraction is also the most likely to contain the broadest scope of bioconcentratable chemicals accumulated from the indoor air.

Partial nephrogenic diabetes insipidus caused by a novel mutation in the AVPR2 gene.

Objective: To identify the molecular basis and clinical characteristics of X-linked congenital nephrogenic diabetes insipidus (CNDI) presenting with an unusual phenotype characterized by partial resistance to AVP.

Subjects: The proband was admitted at the age of 4 years with a history of polydipsia and polyuria since infancy. Initial clinical testing confirmed a diagnosis of diabetes insipidus (DI).

Regulation of arginine vasopressin in the syndrome of inappropriate antidiuresis.

The syndrome of inappropriate antidiuresis (SIAD) is a disorder of sodium and water balance characterized by hypotonic hyponatremia and impaired water excretion in the absence of renal insufficiency, adrenal insufficiency, or any recognized stimulus for the antidiuretic hormone arginine vasopressin (AVP). Hyponatremia is primarily a result of excessive water retention caused by a combination of excessive intake and inappropriate antidiuresis. It is sometimes aggravated by a sodium deficiency caused by decreased intake and/or a secondary natriuresis triggered by and largely corrective of the increase in extracellular volume.

Expression of three different mutations in the arginine vasopressin gene suggests genotype-phenotype correlation in familial neurohypophyseal diabetes insipidus kindreds.

Objective And Study Design: The autosomal dominant form of familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease characterized by a severe and progressive deficiency of AVP secondary to mutations in the gene encoding the AVP precursor. Whereas a number of studies have investigated the pathogenetic mechanisms behind the disease only few studies have included detailed clinical characterization of the affected patients, thereby making genotype-phenotype correlations difficult. The aims of the present study were to investigate the cellular effects of three different adFNDI mutations (A19T, L81P and C110X) by heterologous expression in a neurogenic cell line and to correlate these findings to the corresponding clinical phenotype as determined by extensive clinical tests.

A novel mechanism in recessive nephrogenic diabetes insipidus: wild-type aquaporin-2 rescues the apical membrane expression of intracellularly retained AQP2-P262L.

Vasopressin regulates water homeostasis through insertion of homotetrameric aquaporin-2 (AQP2) water channels in the apical plasma membrane of renal cells. AQP2 mutations cause recessive and dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin. Until now, all AQP2 mutants in recessive NDI were shown to be misfolded, retained in the endoplasmic reticulum (ER) and unable to interact with wild-type (wt)-AQP2, whereas AQP2 mutants in dominant NDI are properly folded and interact with wt-AQP2, but, due to the mutation, cause missorting of the wt-AQP2/mutant complex.

Exposures of preschool children to chlorpyrifos and its degradation product 3,5,6-trichloro-2-pyridinol in their everyday environments.

As part of the Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) study, we investigated the exposures of preschool children to chlorpyrifos and its degradation product 3,5,6-trichloro-2-pyridinol (TCP) in their everyday environments. During this study, the participants were still able to purchase and apply chlorpyrifos at their homes or day care centers. Participants were recruited randomly from 129 homes and 13 day care centers in six North Carolina counties.

Differential cellular handling of defective arginine vasopressin (AVP) prohormones in cells expressing mutations of the AVP gene associated with autosomal dominant and recessive familial neurohypophyseal diabetes insipidus.

An unusual mutation in the arginine vasopressin (AVP) gene, predicting a P26L amino acid substitution of the AVP prohormone, is associated with autosomal recessive familial neurohypophyseal diabetes insipidus (FNDI). To investigate whether the cellular handling of the P26L prohormone differed from that of the Y21H prohormone associated with autosomal dominant inheritance of FNDI, the mutations were examined by heterologous expression in cell lines. Immunoprecipitation demonstrated retarded processing and secretion of the Y21H prohormone, whereas the secretion of the P26L prohormone seemed to be unaffected.

Impaired trafficking of mutated AVP prohormone in cells expressing rare disease genes causing autosomal dominant familial neurohypophyseal diabetes insipidus.

Objective And Study Design: Two different mutations in the arginine vasopressin (AVP) gene associated with autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) predict Y21H (AVP2) and V67A (NP36) amino acid substitutions of the AVP prohormone. They are unique in that they change, respectively, the AVP moiety and a region of the neurophysin II domain not so far affected by any mutations. To test whether they affect the cellular handling of the AVP prohormone in a similar manner to previously investigated mutations, they were examined by heterologous expression in cell lines.

Six novel mutations in the arginine vasopressin gene in 15 kindreds with autosomal dominant familial neurohypophyseal diabetes insipidus give further insight into the pathogenesis.

Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is caused by postnatal arginine vasopressin (AVP) deficiency resulting from mutations in the AVP gene encoding the AVP pre-prohormone. To advance the understanding of adFNDI further, we have searched for mutations in the AVP gene in 15 unrelated kindreds in which diabetes insipidus appeared to be segregating. In nine kindreds, seven different previously described mutations were identified.

Autosomal dominant neurohypophyseal diabetes insipidus due to substitution of histidine for tyrosine(2) in the vasopressin moiety of the hormone precursor.

The autosomal dominant form of familial neurohypophyseal diabetes insipidus (adFNDI) has been linked to 40 different mutations of the gene encoding the vasopressin-neurophysin II (AVP-NPII) precursor. All of these mutations have been located in either the signal peptide or neurophysin II moiety. We now report a three-generation Turkish kindred in which severe adFNDI cosegregates with a novel missense mutation in the part of the AVP-NPII gene encoding the AVP moiety.

Clinical and molecular analysis of three families with autosomal dominant neurohypophyseal diabetes insipidus associated with a novel and recurrent mutations in the vasopressin-neurophysin II gene.

Objective: To test further the hypothesis that autosomal dominant neurohypophyseal diabetes insipidus (adFNDI) is caused by heterozygous mutations in the vasopressin-neurophysin II (AVP-NPII) gene that exert a dominant negative effect by producing a precursor that misfolds, accumulates and eventually destroys the neurosecretory neurons.

Methods: Antidiuretic function, magnetic resonance imaging (MRI) of the posterior pituitary and AVP-NPII gene analysis were performed in 10 affected members of three unreported families with adFNDI.

Results: As in previously studied patients, adFNDI apparently manifested after birth, was due to a partial or severe deficiency of AVP, and was associated with absence or diminution of the hyperintense MRI signal normally emitted by the posterior pituitary, and with a heterozygous mutation in the AVP-NPII gene.