Dilatative Uropathy as a Manifestation of Neurohypophyseal Diabetes Insipidus due to a Novel Mutation in the Arginine Vasopressin-Neurophysin-II Gene

Abstract

Background

Polydypsia and polyuria are frequent symptoms in patients with sellar masses caused by neurohypophyseal diabetes insipidus. Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI), a disorder caused by mutations in the arginine vasopressin (AVP) ­neurophysin II (NPII) gene, should be considered as a rare differential diagnosis. A delayed diagnosis bears the risk of life-threatening electrolyte imbalances and permanent urinary tract damage, leading to impaired quality of life.

Patients:

We present a Caucasian kindred of at least 4 generations with FNDI.

Methods:

Clinical histories, endocrine para­meters, and results of molecular analyses of the AVP gene are presented with a review of the literature on diabetes insipidus (DI) related urinary tract dilatation.

Results:

Polyuria and polydipsia were only reported based on explicit and thorough interrogation after more than 4 years of clinical follow-up. A novel heterozygous mutation in the AVP gene was found in all examined symptomatic subjects (c.1-33_c.4del37nt). A literature review revealed that non-obstructive hydronephrosis (NOH) is a rare but known complication of DI.

Conclusions:

Since increased fluid intake is often a typical familial pattern in adFNDI, it is frequently missed as being pathologic in affected patients, therefore a detailed clinical history of drinking volumes is of critical importance. AVP gene testing is an important component in the confirmation of the diagnosis. Otherwise unexplainable NOH should lead to further investigations and evaluation of rare diseases like FNDI.

Zusammenfassung

Hintergrund:

Polyurie und Polydypsie auf­grund eines Diabetes insipidus neurohormonalis sind häufige Leitsymptome sellärer Raumforderungen. Der autosomal dominante familiäre neurohypophysäre Diabetes insipidus (adFNDI) – eine durch Mutationen im Arginin-Vasopressin-(AVP)-Neurophysin II–Gen verursachte Erkrankung – stellt eine seltene Differenzialdiagnose dar. Eine verzögerte Diagnosestellung birgt nicht nur das Risiko lebensbedrohlicher Elektrolytverschiebungen, sondern auch nicht-reversibler Schäden der ableitenden Harnwege und eingeschränkter Lebensqualität.

Patienten:

Wir stellen eine kaukasische Familie mit FNDI in mindestens 4 Generationen vor.

Methoden:

Die Anamnesen, Laborparameter, molekulargenetischen Untersuchungsergebnisse des AVP-Gens und eine Literaturrecherche zu Veröffentlichungen über Diabetes insipidus-(DI)-assoziierte Dilatationen der ableitenden Harnwege werden vorgestellt.

Ergebnisse:

Erst nach 4 Jahren expliziter und wiederholter Nachfrage wurden die Symptome Polyurie und -dipsie angegeben. Eine neue he­terozygote Mutation im AVP-Gen wurde in allen symptomatischen Patienten nachgewiesen (c.1-33_c.4del37nt). Im Rahmen der Literaturrecherche zeigte sich, dass nicht-obstruktive Hydronephrosen eine bekannte seltene Kom­plikation eines DI sind.

Schlussfolgerung:

Da hohe Trinkvolumina in Familien mit adFNDI normal sind, werden sie oft nicht als pathologisch und berichtenswert ange­sehen. Deshalb ist eine detaillierte anamnestische Erhebung der Trinkvolumina essenziell. Die Untersuchung des AVP-Gens ist eine wichtige Komponente der Diagnosesicherung. Ätiologisch ungeklärte, nicht-obstruktive Uropathien sollten Anlass für eine weiterführende Diagnostik und Ausschluss seltener Erkrankungen wie adFNDI sein.

Key words

diabetes insipidus - hydronephrosis - AVP neurophysin-II gene mutation - clinical history - AVP gene testing - pediatric neurooncology

Schlüsselwörter

Diabetes insipidus - Hydronephrose - AVP-Neurophysin-II-­Mutation - Anamnese - Untersuchung des AVP-Gens - pädiatrische Neuroonkologie

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