Novel AVPR2 mutations and clinical characteristics in 28 Chinese families with congenital nephrogenic diabetes insipidus.

AIMS: To investigate genotype and phenotype of congenital nephrogenic diabetes insipidus caused by AVPR2 mutations, which is rare and limitedly studied in Chinese population. METHODS: 88 subjects from 28 families with NDI in a department (Beijing, PUMCH) were screened for AVPR2 mutations. Medical records were retrospectively reviewed and characterized. Genotype and phenotype analysis was performed. RESULTS: 23 AVPR2 mutations were identified, including six novel mutations (p.Y117D, p.W208R, p.L313R, p.S127del, p.V162Sfs*30 and p.G251Pfs*96). The onset-age ranged from 1 week to 3 years. Common presentations were polydipsia and polyuria (100%) and intermittent fever (57%). 21% and 14% of patients had short stature and mental impairment. Urine SG and osmolality were decreased, while serum osmolality and sodium were high. Urological ultrasonography results showed hydronephrosis of the kidney (52%), dilation of the ureter (48%), and thickened bladder wall or increased residual urine (32%), led to intermittent urethral catheterization (7%), cystostomy (11%) and binary nephrostomy (4%). Urological defects were developed in older patients. Genotype and phenotype analysis revealed patients with non-missense mutations had higher levels of serum sodium than missense mutations. CONCLUSION: In the first and largest case series of NDI caused by AVPR2 mutations in Chinese population, we established genetic profile and characterized clinical data, reporting six novel mutations. Further, we found genotype was associated with phenotype. This knowledge broadens genotype and phenotype spectrum of rare congenital NDI caused by AVPR2 mutations, and provides basis for studying molecular biology of AVPR2.

Hypertensive urgency in nephrogenic diabetes insipidus with concomitant Hinman syndrome.

Diabetes insipidus is a syndrome characterised by the inability to conserve water or concentrate urine, leading to excessive excretion of urine. In congenital nephrogenic diabetes insipidus (CNDI), common presentations include failure to thrive, polydipsia, polyuria and dehydration. The long trajectory of the disease, coupled with psycho-behavioural changes as a child grows, can precipitate a period of non-adherence despite initial optimal control, especially in the adolescent age group. Social inconvenience of repeated voiding and nocturnal disturbances can lead to adapted urine holding behaviour, also known as non-neurogenic neurogenic bladder (Hinman syndrome). Anatomical changes in the urinary system, such as bladder trabeculation and hydroureteronephrosis, can subsequently give rise to functional renal impairment. We present a case of CNDI with concomitant Hinman syndrome, resulting in acute renal impairment and hypertensive emergency. We aim to raise awareness of the association between these two entities.

Cognitive and psychosocial functioning of patients with congenital nephrogenic diabetes insipidus.

Mental retardation (MR) is generally considered one of the main complications of congenital nephrogenic diabetes insipidus (NDI). However, psychometric studies of NDI patients are scarce and outdated. In the present study, 17 male NDI patients underwent psychological evaluation. Total intelligence quotient of 14 patients was within (n = 13) or above (n = 1) the normal range, 1 patient had an intelligence score between -1 and -2 standard deviations (S.D.) and 2 young patients had a general cognitive index more than 2 S.D. below the norm. Attention deficit hyperactivity disorder criteria were met by 8 out of 17 patients and scores on short-term memory were low in 7 out of 10. No relation between test performances and age at diagnosis or hypernatremia could be found, with the exception of a negative correlation between age at start of therapy and verbal IQ in one age group. Although several explanations for an association between MR and NDI can be postulated, it seems that the current prevalence of MR among patients with this disease is considerably lower than suggested in literature.

Transient nephrogenic diabetes insipidus accompanied by possible psychogenic polydipsia.

A 50-year-old Japanese man had been suffering from polydipsia and polyuria for 2 months without any other specific symptoms. His daily urinary output reached 5 liters. On admission, no abnormalities of the kidneys, heart, thyroid, adrenals, pituitary or hypothalamus were detected by laboratory tests and MRI of the head. Pure psychogenic polydipsia was ruled out because his urine volume did not decrease sufficiently with 18 h of water deprivation and the subsequent injection of aqueous vasopressin. Plasma arginine vasopressin (AVP) levels against plasma osmolality remained within the normal range during the test. These results indicated that diabetes insipidus in this case was caused by renal insensitivity to AVP. The symptoms disappeared spontaneously, and marked improvement was observed in a second water deprivation test 1 month later, although the maximum urine concentration was still subnormal. The combination of both latent insufficiency of AVP secretion and impairment of the renal countercurrent system induced by psychogenic polydipsia was speculated as a possible mechanism for the transient nephrogenic diabetes insipidus in this case.