Zaki et al. (2006) described a rare case of an autosomal recessive NDI harboring a new AQP2 mutation, who developed a renal cell carcinoma. The 50-day old Bedouin Arab girl was born to healthy consanguineous parents who subsequently had five healthy children. She presented with fever, vomiting, refusal of feeding, and poor weight gain. She was found to be dehydrated and weak, and have an elevated serum sodium concentration (159 mmol/l). The hypernatrenemia and dehydration was corrected with fluid substitution. However, within 2-weeks she was readmitted with fever, lethargy, and dehydration. She had no history of vomiting or diarrhea this time. Serum sodium was still found to be elevated (165 mmol/l). Urine osmolality was 17mmol/Kg, while serum osmolality was 294. Intranasal administration of vasopressin did not cause any change in the osmolality. Over a 12-hour period, she passed about 700 ml of urine. She was initially diagnosed with nephrogenic diabetes insipidus, most likely autosomal recessive, considering the female gender and paternal consanguinity. Molecular genetic analysis was conducted to confirm the diagnosis. Sequencing of the AQP2 gene revealed a novel missesnse homozygous mutation, p.Ile107Asn, for which both parents were found to be heterozygous. The child was treated with hydrochlorothiazide (3 mg/kg/day) and indomethacin (3 mg/kg/day). However, long-term indomethacin therapy was discontinued because of significant gastric irritation. The patient showed an initial period of normal psychomotor development. However, she deteriorated after this. At 7-years of age, her psychomotor development was 12-months retarded, while height and weight were below the 3rd centile. CT scan of the brain revealed bilateral symmetric calcification of the basal ganglia as well as calcification at the junction between the white and grey matter in the parietal region. At the age of 16 years, she was found to have a right renal mass, which proved to be a renal cell carcinoma (stage T1 N0 M0) and radial nephrectomy was performed. After >1 year, no tumor recurrence was detected in a follow-up computed tomography scan and the patient is under continuous surveillance by ultrasonography every 3 months. At the time of reporting, she was not on any drug therapy (patient and family refused any medication) and continues to pass 6-7 l urine per day. Her weight and height were 41 kg and 150 cm, respectively (both below the 5th percentile for the corresponding age). Zaki et al. (2006) proposed that the occurrence of autosomal recessive NDI together with a renal cell carcinoma may be of unrelated coincidence, one has to consider thiazide diuretics as one possible cause.

In 2008, Al-Kandari et al. reported a child with intracranial calcification complicating central diabetes insipidus.

Van Lieburg et al. (1994) reported a Palestinian patient with NDI. He was born of consanguineous parents with no family history of NDI. Two siblings of the proband's mother died as adults, of causes not related to NDI. At age 6 week the proband 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. When at age of 7 months, he was severely dehydrated (Na 186 mmol/liter, serum osmolality 429 mOsm/kg), but urine osmolality was low (150 mOsm/kg). Intravenous administration of lysine vasopressin did not result in an increase of urine osmolality. As an adult, he drank 7-10 liters/day (no medication). At the molecular level, this patient was found to be homozygous for a 1-bp deletion (369delC) in the AQP2 gene.

Hochberg et al. (1997) identified two inbred kindreds of Bedouin Arab origin, with a total of 11 patients with NDI. Both kindreds had an extremely high degree of consanguinity. The most common presenting symptoms in these patients were neonatal fever and vomiting (6) and failure to thrive (4). Clinical features in the patients included fetal distress short stature, slow psychomotor development, and mental retardation. One patient showed psychosis, which was probably thirst related. Diagnosis of NDI was made based on the finding of polyuria, low urine osmolality, high plasma osmolality, high serum sodium concentrations, and lack of response to vasopressin. Molecular analysis revealed probands in both kindreds to be homozygous for a novel mutation (G298T) in the AQP2 gene. It was not clear if the two kindreds were related.

Carroll et al. (2006) identified two novel missense mutations in the AQP2 gene in Arab families with nephrogenic diabetes insipidus.