IMPE Abstracts

Genetic forms of central diabetes insipidus have been described in patients with mutations in the AVP gene (autosomal dominant or recessive) and in the WFS1 gene (Wolfram Syndrome, autosomal recessive). Autosomal dominant forms are the result of mutations in the portion of the AVP gene that codes for the peptide Neurophysin II (NPII). Pathogenesis is related to the toxic cellular effect of the mutated protein. Although clinical presentation is usually in the pediatric age, variability can be seen even in members of the same family.

Case reports: Index case: 18-month-old male who presented polyuria and polydipsia since 6 months old. Antecedents: extreme prematurity with gestational age 26 weeks and birth weight 1160 g. Neonatology hospitalization without notable complications, two hospitalizations for bronchiolitis without dehydration in first year of life, daily intake of 1 liter of milk and 2 liters of water, mildly delayed milestones, interrupted sleep, and appropriate growth (weight at 10^th percentile, height at 50^th percentile). During the evaluation, diuretic rhythm was 13 ml/kg/h, fasting natraemia 148 mEq/L with an appropriate response to desmopressin intake with decrement in natraemia to 135 mEq/L and diuresis to 3 ml/kg/h. MRI showed absent neurohypophysis hyper intense signal. Regular DDAVP treatment was started at 2 years and 3 months with decreased diuresis and fluid intake without complications. His mother reported 3-4 liters’ intake per day, but when evaluated, natremia was 142 mEq/l, plasma and urinary osmolarity 278 mOsm/L and 146 mOsm/L respectively. She refused to perform a water restriction test His maternal grandfather referred to be polyuric and polydipsic since infancy. Six months after diagnosis of the index case, a water restriction test was performed, showing inability to concentrate urine. In the child, the AVP gene was studied through an NGS panel. A previously undescribed probably pathogenic variant was found in c.298G>C in heterozygous in exon 2. This variant involves a substitution of alanine for proline at codon 100. It is found in a hot spot region and in silico models predict function alteration. Conclusion: a new pathogenic variant in the AVP gene is presented in a family with several members with suspected central diabetes insipidus.