P291\u2005Nephrogenic diabetes insipidus in a female infant

Abstract

Aim Nephrogenic Diabetes Insipidus(NDI) is rare. 90% of cases are due to a defect in the AVPR2 gene which is widely believed to be inherited in an X-linked recessive pattern; from asymptomatic carrier mothers, to severely affected sons, but not daughters. Other, less common cases (∼1% of NDI cases), are inherited in an autosomal dominant pattern due to a defect in the AQP2 gene. However, our case will demonstrate how females can present with symptomatic NDI secondary to AVPR2 mutation. Methods This is a case study of a 14-month-old girl who was referred to the Paediatric Outpatient Department with a history of faltering growth, excessive drinking and plentiful wet nappies. At birth she plotted on the 50th centile for weight but subsequently dropped to the 9th. Weaning was a difficult, with her preferring liquids to solids. Moreover, excessive thirst resulted in her drinking water from the swimming pool, bath water and even the dog’s bowl. Serum electrolytes, in addition to serum and urine osmolality and a desmopressin test, confirmed the diagnosis of NDI. There was positive family history with the patient’s Father having NDI, treated initially with diuretics then desmopressin until age 14, and since no longer requiring medication. An assumption was made that the patient thus acquired NDI via autosomal dominant inheritance of AQP2 gene. However, genetic tests were not performed at this stage. Results The patient’s Father was found to be hemizygous for AVPR2 gene. Genetic testing then revealed the patient to be a carrier of AVPR2 gene. Inherited via X-linked recessive form this would not normally affect females. Nevertheless, due to lyonisation of×chromosome this patient was symptomatic. Conclusion X-linked autosomal recessive disorders can also affect females. This is due to the process of lyonisation, which in itself has different forms and causes. Appreciation of lyonisation defect is crucial in the diagnosis and family counselling of patients with X-linked recessive disorders such as NDI, in addition to other more common disorders such as Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD), Duchenne Muscular Dystrophyor Haemophilia.