1998 Global Conference Proceeding

March 02 - 04, 1998

Conference: 1998 Global Conference
Title: Nephrogenic Diabetes Insipidus in a Palestine Sibship
Authors: Mallmann, Rudolf; van Lieburg, Angenita; Monnens, Leo A.H.
Institutions: Elisabeth-Krankenhaus, University of Nijmegen, University Hospital Nijmegen

At age 6 weeks the third son of an otherwise healthy family of Palestine descent presented with feeding difficulties, insufficient weight gain, and fever. Polyuria with low urine osmolality and a decrease of body temperature after administration of large fluid volumes were noticed. The diagnosis of NDI was only made at the age of 7 months when he was seen in our hospital with severe dehydration and hypernatremia. Intravenous administration of lysine vasopressin did not result in an increase of urine osmolality. Despite several treatment modalities over the years including indomethacin and hydrochlorothiazide his fluid needs have always been very high. Now, as an adult, he drinks 7 - 10 liters/day without any medication.

In his niece, the daughter of his older brother, NDI was diagnosed at age 5 weeks during her first attack of hypersalemic dehydration. Rehydration of this young girl was difficult, covering a period of several weeks. Neither indomethacin nor hydrochlorothiazide alone or in combination did alter the girl's fluid demands which were about 2.5 liters at age 4 months. In both patients a C369 deletion in the aquaporin 2 gene could be demonstrated. The asymptomatic parents and brothers of the first patient as well as the mother of the young girl were found to be heterozygous for this defect. His sister was homozygous for the normal allele.

A male of Palestinian descent, now grown, was diagnosed with nephrogenic diabetes insipidus (NDI) at seven months of age. He had been exhibiting symptoms of NDI and having life-threatening attacks of dehydration since he was six weeks old. Different treatments were tried but did not prove effective. His niece, the daughter of his older brother, was diagnosed as having NDI when she was five weeks old. Neither indomethacin nor hydrochlorothiazide were able to reduce her high water demands. Both patients had the same mutation, a C369 deletion, in their aquaporin 2 gene which means a part of the gene's genetic sequence was missing. The parents of the adult patient as well as his older brother and sister are heterozygote for this mutation, which means they carry the mutation paired with the non-mutated form of the gene. This confirms the recessive mode of inheritance for this form of inherited NDI, which means the mutation resulting in NDI is incapable of expression unless the mutated gene responsible for the NDI is carried by both parents.