1999 European Regional Conference Proceeding

May 12 - 16, 1999

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Conference: 1999 European Regional Conference
Title: Follow up of NDI patients and presentation of a case report
Authors: Procaccio, Mirella; Curcio, C; Cesareo, Layla; Albertazzi, Elena; Chini, Bice; Faranda, Sara; Frattini, Annalisa; Vezzoni, Paolo; Fossali, E; Appiani, A; Natale, B. Di; Lukesich, M.; Livolti, S.; Rosini, A.; Einaudi, S.; Pecoraro, C.; Miglietti, N.; Razzoli, E.; Maggi, M.; Bettinelli, Alberto
Institutions: University of Milan, Consiglio Nazionale delle Ricerche Cellular and Molecular Pharmacology Center, CNR Institute of Neuroscience, Consiglio Nazionale delle Ricerche Institute of Advanced Biomedical Technologies, Istituto Tecnologie Biomediche Avanzate - ITBA, CNR-ITBA, Istituti Clinici di Perfezionamento, Hospital Regina Margherita, University of Catania, Department of Pediatrics, University of Napoli, Department of Endocrinology, University of Brescia
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Nephrogenic diabetes insipidus (NDI) is a rare, congenital disease, characterized by resistance of distal tubules and collecting ducts of the nephrons to the antidiuretic hormone arginine vasopressin (AVP), resulting in the production of large quantities of diluted urine. Congenital NDI has two patterns of transmission: autosomal and X-linked. The X-linked recessive form is the most frequent and it is caused by mutations in the gene encoding for the vasopressin V2 receptor (AVPR2). Today, it is possible to confirm the clinical diagnosis with the molecular identification of the genetic defect, and to recognize the different forms of NDI from other tubulopathies that might have, at the onset, similar clinical presentations.

We examined 17 patients whose clinical history of NDI was confirmed by the identification of a mutation in the AVPR2 gene. The mean age at diagnosis was 1.4 ± 3 years (range 15 days ÷ 13.5 years) and the main symptoms at clinical presentation were polyuria, polydipsia, vomiting, failure to thrive, fever and anorexia. All the patients had hypernatremia (Na+ =156.7 ± 7.4 mEq/L; range 145÷174) and an impaired response of urinary osmolarity after somministration of exogenous DDAVP (urinary osmolarity after stimulus 165.5 ± 126 mOsm/L). In order to evaluate the growth of our NDI patients, we collected auxologycal data of weight and height at diagnosis and during the follow-up; we then draw growth graphics, corrected with parent's height, on Tanner and Whitehouse's cards. We finally transformed growth data in standard deviation scores (SDS), in order to evaluate the failure to thrive. At diagnosis, the SD scores (SDS) were -1.66 ± 1.76 (range -4.8÷1.6) and -2.64 ± 2 (range -5.9÷0.7) for height and weight respectively; the SDS for the weight for height parameter was -1.4±2.1 (range -3.2÷4.7). After a follow-up of 8 ±5 years, however, we observed an improvement of the growth curves, with a -0.8 ± 1.1 SDS for height, a -0.7 ± 1.8 SDS for weight, and a weight for height SDS of 0.26±2.4.

Finally, we will present a case report of a patient with clinical symptoms and laboratory's data typical of X-linked NDI. However, since the patient resulted negative for AVPR2 mutations, his clinical history was reconsidered and a diagnosis of Bartter disease, confirmed by genetic analysis, was made. This case underlies the importance of combining clinical and molecular approaches for the diagnosis of congenital tubulopathies.

Nephrogenic diabetes insipidus (NDI) is characterized by the kidney's inability to respond to the antidiuretic hormone, arginine vasopressin (AVP). NDI patients experience polyuria (chronic passage of large volumes of urine) and polydipsia (chronic excessive thirst). Congenital NDI may be transmitted either by a mutation on the X-chromosome or an autosomal chromosome. X-linked NDI is by far the most common form of congenital NDI.

Casareo, et al., performed a long-term study of 17 patients whose NDI was confirmed by the identification of a mutation in their respective vasopressin-2 receptor AVPR2) gene. The mean age at diagnosis was 1.4 + or - 3 years, and the main symptoms when they were first presented for diagnosis were polyuria, polydipsia, vomiting, failure to thrive, fever and anorexia. All patients had abnormally high levels of plasma sodium and all failed to respond to dDAVP administration.

The researchers recorded the weight and height of the patients at their time of diagnosis. They recorded them again 8.5 years after the initial measurements. The latter measurement showed an improvement in the patients' growth curves.

The researchers also presented a case report of a patient whose symptoms and laboratory data were typical of X-linked NDI. However, the patient had no AVPR2 gene mutation. Rediagnosis showed the patient had Bartten disease. This case illustrates the importance of combining classical and molecular approaches for the diagnosis of congenital diseases involving the kidney's tubules.