Skip to main content
Public beta This website is in public beta – please give your feedback.
Endocrinology

Presentation: Patient with possible familial AVP-related polyuria

Arginine vasopressin (AVP) related polyuria, which includes AVP-deficiency and AVP-resistance, has a prevalence of 1 per 25,000 population. Hereditary AVP-deficiency accounts for approximately 1% of all AVP-deficiency cases. Hereditary AVP-resistance has an estimated incidence of approximately 1 per 1,000,000.

Example clinical scenario

A 16-year-old female presents with excessive thirst and passing large volumes of pale urine. She has had symptoms since she was five years old but never consulted a doctor. She has three siblings, as well as two cousins who have been diagnosed with AVP-deficiency and are on desmopressin. Her father has not sought medical attention but is always thirsty and passes large volumes of pale urine. Investigations reveal 24h urine volumes 6.3L per day, serum osmolality 301mOsmol/kg, urine osmolality 78mOsmol/kg.

When to consider genomic testing

All patients with a diagnosis of AVP-related polyuria should be offered genomic testing if both the following criteria are met:

  • clinical signs, symptoms and biochemical features consistent with a diagnosis of AVP-related polyuria (relevant history and biochemistry results should be provided on the test request form to aid interpretation of the genetic results); and
  • exclusion of acquired causes of AVP-related polyuria including primary polydipsia, trauma, malignancy, infection, autoimmune disease and drugs (e.g. antibiotics, antifungals and antiviral agents).

Genomic testing is more likely to be indicated with any of the following:

  • patients presenting with features of AVP-related polyuria before the age of 20;
  • patients with a relevant and positive family history; and/or
  • difficulty differentiating between AVP-deficiency and AVP-resistance.

All patients with a diagnosis of AVP-related polyuria and features of renal tubulopathy, such as Bartter syndrome and Gitelman syndrome, should be offered genomic testing.

What do you need to do?

  • Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
  • For patients who meet test directory eligibility criteria presenting with features of AVP-related polyuria without any other features suggesting a renal tubulopathy, select the following:
    • R440.1 Hereditary isolated diabetes insipidus small panel. This panel comprises of the following genes: AVP, AVPR2, and AQP2. This test detects small variants and copy number variation (CNV) by small gene panel sequencing.
  • For patients who meet test directory eligibility criteria presenting with features of AVP-related polyuria with features of a renal tubulopathy, select the following:
    • R198.1 Renal tubulopathies (whole exome sequencing or medium panel sequencing). This panel comprises of the following genes: AP2S1, AQP2, ATP1A1, ATP6V0A4, ATP6V1B1, AVPR2, BSND, CA2, CASR, CLCNKB, CLDN10, CLDN16, CLDN19, CNNM2, CTNS, CUL3, CYP24A1, FAH, GATM, GNA11, HNF1B, HNF4A, KCNJ1, KCNJ10, KCNJ16, KLHL3, MAGED2, NR3C2, REN, RRAGD, SARS2, SCNN1A, SCNN1B, SCNN1G, SEC61A1, SLC12A1, SLC12A3, SLC22A12, SLC2A2, SLC2A9, SLC4A1, SLC4A4, SLC5A2, TRPM6, UMOD, VIPAS39, VPS33B, and WNK4. This test detects small variants and copy number variation (CNV) by whole exome sequencing or medium gene panel sequencing.
  • For patients presenting with features of AVP-related polyuria in whom a genetic diagnosis in an AVP, AVPR2 or AQP2 gene has been established in another family member, single gene testing for that specific variant should be considered.
  • None of the tests described above includes whole genome sequencing, so you should use your local Genomic Laboratory Hub test order and consent (record of discussion) forms.
  • These tests are DNA-based, and an EDTA sample (typically a purple-topped tube) is required. The sample is best stored at 4°C until it can be posted to the genomic laboratory.
  • Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

Resources

For clinicians

References:

For patients

↑ Back to top
  • Last reviewed: 07/05/2025
  • Next review due: 07/05/2026
  • Authors: Dr Shailesh Gohil, Professor Márta Korbonits, Professor Miles Levy, Jayden Wong
  • Reviewers: Dr Louise Izatt