Autosomal recessive familial neurohypophyseal diabetes insipidus: Onset in early infancy

Abdulsalam Abu Libdeh, Floris Levy-Khademi, Maha Abdulhadi-Atwan, Emily Bosin, Mira Korner, Perrin C. White, David H. Zangen

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Background: Familial neurohypophyseal diabetes insipidus (FNDI), usually an autosomal dominant disorder, is caused by mutations in the arginine vasopressin (AVP)-neurophysin II preprohormone leading to aberrant preprohormone processing and gradual destruction of AVP-secreting cells. Patients typically present between 1 and 6 years of age with polyuria and polydipsia. Objective: Clinical, biochemical, and genetic studies of three new cases of autosomal recessive FNDI presenting in early infancy. Patients: Three Palestinian cousins presented with failure to thrive, vomiting, irritability, and fever. The parents were asymptomatic. Patients developed hypernatremia (154-163 mmol/l) and serum hyperosmolality (>320 mOsm/kg), while urine osmolality remained between 73 and 229 mOsm/kg. Plasma AVP levels were low, and the posterior pituitary bright spot was absent on magnetic resonance imaging (MRI). All patients responded to desmopressin. Results: Patients were homozygous and parents were heterozygous for microsatellite markers flanking the AVP gene. All patients were homozygous for the P26L (proline to leucine) substitution affecting mature AVP. A founder effect with the single original kindred carrying the P26L mutation was confirmed by microsatellite analysis, but patients in that family presented only at 2 years of age. In microsatellite analysis, the new kindred patients were not homozygous and did not share a single allele at the aquaporin 2 and vasopressin receptor-2 genes locuses. Conclusion: This is the first description of autosomal recessive FNDI presenting in the neonatal period. The unusual early clinical and radiological (MRI) presentation argues against gradual destruction of AVP-secreting neurons as the pathophysiological mechanism. Factors beside allelism of AVP-related genes must influence the age of FNDI presentation given the founder effect demonstrated for the P26L mutation.

Original languageAmerican English
Pages (from-to)221-226
Number of pages6
JournalEuropean Journal of Endocrinology
Issue number2
StatePublished - 1 Feb 2010
Externally publishedYes


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