ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 65 P308 | DOI: 10.1530/endoabs.65.P308

Making best use of clinical genetic testing in the diagnosis of Neurohypophysial Diabetes Insipidus with significant family history - a case for early access

Shehla Siddiqui & Emanuela Filipas

East and North Herts Institute of Diabetes and Endocrinology, Stevenage, UK

Background: Familial Diabetes Insipidus is a very rare entity and can have either neurohypophyseal (FNDI) or nephrogenic forms with different transmission patterns. FNDI accounts for less than 5% of the 1:25 000 cases of DI diagnosed in UK. It is usually an autosomal dominant disorder caused by mutations in AVP (arginine vasopressin) gene, which regulates the vasopressin hormone synthesis; its signs and symptoms of polyuria & polydipsia usually become apparent in childhood and worsen over time.

Case presentation: We describe the case of a 46 years old female presenting with polydipsia 20–30 l of fluids/day, polyuria and nocturia 3–6 times per night ever since early childhood. She had very convincing similar family history in all generations on her paternal side, affecting nine first- and second-degree relatives, however no formal diagnosis was previously attempted. Initial biochemistry results showed dilute urine at 77 mOsm/kg, serum osmolality 295 mosm/kg, otherwise normal pituitary hormones. Patient had supervised water deprivation test (WDT), during which serum osmolality rose to 302 mOsmol/kg after one hour, with urine osmolality of 74 mOsmol/kg. 2 ug desmopressin administration intramuscularly achieved good but incomplete concentration in urine osmolality to maximum of 436 mOsm/kg at 4 h. Patient commenced desmopressin tablets with good symptomatic response on a total split dose of 300 mcg daily. Considering the significant family history, her son was offered endocrine testing and WDT, with a view to formal molecular genetic testing being considered subsequently.

Conclusion: WDT causes apprehension in children and parents, which often delays presentation to medical services and appropriate treatment initiation. The utility of genetic testing in confirming underlying familial CDI has previously been acknowledged, even in the absence of definite biochemical features. Its advantages include appropriate family counselling as well as affordable cost, and clinicians should be aware of benefits of early access to this for affected family members.

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