Nephrogenic Diabetes Insipidus Presenting with Developmental Delay and Intracranial Calcification Anurag Bajpai, Madhulika Kabra, Rohini Thapliyal, Sheffali Gulati and Veena Kalra

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Abstract. A one-year-boy presented with constipation, fever, failure to thrive and developmental delay from the neonatal period. Investigations revealed persistent hypernatremia and deranged renal functions. Diagnostic work-up was suggestive of nephrogenic diabetes insipidus (NDI). Computerized tomography of head revealed calcification in the frontal, thalamic and basal ganglia region. The rare association of NDI and intracranial calcification is discussed. [Indian J Pediatr 2005; 72 (6) : 527-528]

Key words : Developmental delay; Intracranial calcification; Nephrogenic diabetes insipidus

Nephrogenic diabetes insipidus (ND1), a disorder of resistance to action of anti diuretic hormone (ADH), is characterized by polyuria, polydipisa, low urine osmolality and high serum osmolalityL Intracranial calcifications have only rarely been reported in children with NDI. An infant who presented to us with developmental delay, constipation, fever and intracranial calcification was diagnosed as NDI.

CASE REPORT

This one-year-old boy presented to us with constipation, failure to thrive and recurrent vomiting from the neonatal period. He had delayed development and at the age of one year was not able to stand with support and could speak only disyllables. The child had low grade fever (99- 100~ off and on since the age of 3 months without any localizing features. On examination he was alert and active with a pulse rate of 110/rain, respiratory rate of 36/ min and blood pressure of 90/50 mm Hg. His weight (6.1 kg) and length (63 cm) were less than 3 rd percentile for age. Developmental assessment revealed mild developmental delay (DQ- 75). Systemic examination was normal.

Investigations showed high serum levels of sodium (174 mEq/L) with normal potassium levels (3.8 mEq/L). Renal functions were deranged with urea of 104 mg/dl and creatinine of 0.9 mg/dl. Liver function tests, serum calcium, phosphate, alkaline phosphatase and thyroid profile were normal. Work-up for recurrent vomiting (gastroesophageal reflux study, barium swallow and abdominal ultrasound) and deranged renal functions (~Tc dimercaptosuccinic acid scan, ultrasound for kidney and

Correspondence and Reprint requests : Dr. Professor Veena Kalra, Head of Department, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi-110029.

urinary bladder) were normal. Computer ized tomography (CT) scan of the head revealed calcification in the frontal, thalamic and basal ganglia region (Fig. 1).

Fig 1. Computerized scan of head showing intarcerebral caification in the frontal lobe and thalamus.

The most striking finding in the case was persistent hypernatremia (serum sodium- 160-182 mEq/L). There was no history of polyuria; 24-hour collection of urine in hospital however documented the same (> 7 ml/kg/hr). Elevated serum sodium levels (157-182 mEq/L) were associated with elevated plasma osmolality (341-381 mOsm/L) and low urine osmolality (158-282 mOsm/L). Based on the findings of polyuria, high serum sodium and plasma osmolality with low urine osmolality a diagnosis of diabetes insipidus was considered and vasopressin

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response test per formed. Failure to increase ur inary osmolality one hour after intramuscular injection of 5 units vasopressin (increase from 158 m O s m / L to 185 m O s m / L ) wi th p lasma osmola l i ty of 320 m O s m / L suggested diagnosis of nephrogenic DI. Evaluation for secondary causes for nephrogenic DI in the form of serum potassium, calcium, urine calcium to creatinine ratio, ul t rasound and 99Tc DMSA scan for kidneys was non- con t r ibu to ry . The child was s ta r ted on hydrochlorothiazide (3 mg/kg /day) , amiloride (0.3 m g / kg/day) and indomethacin (3 mg/kg /day) . Mother was instructed to give more than one liter of fluids in the form of water and milk eve ry day. These measures were associated with decrease in urine output (3 ml /kg /h r ) , increase in urine osmolality (525 mOsm/L), decrease in serum sodium (143 mEq/L) and normalization of renal parameters (urea 40 mg/d l , creatinine-0.4 mg/dl ) over a period of 2 weeks. At two-months of follow-up the child had gained 1.5 kg weight and had normal levels of serum sodium (136 mEq/L) , urine osmolality (540 mOsm/L) and renal functions (urea 20 mg/dl , creatinine 0.3 mg/dl).

DISCUSSION

Nephrogen ic diabetes ins ipidus is charac ter ized by decreased responsiveness of distal tubule and collecting duct to antidiuretic hormone (ADH)L Resistance to action of ADH as in NDI is associated with increased loss of free water, polyur ia , low urine osmolal i ty and increased serum osmolality 2. Most children with NDI have defects in the action of V2 receptor, a disorder inheri ted in X l inked fashion. Early age of onset and exclusion of secondary causes of NDI in the present case indicates the diagnosis of primary NDI.

NDI usually presents with polyuria and polydipsia. H o w e v e r in infants po lyu r i a and po lyd ips i a is u n c o m m o n and p r e sen t a t i on is wi th fea tu res of dehydration like fever, constipation, vomiting, failure to thrive and developmental delay 3. The diagnosis is usually delayed till hypernatremia is noted. This highlights the importance of high index of suspicion and early diagnosis of diabetes insipidus in the infantile period.

Management of children with NDI requires education of parents regarding the importance of liberal oral fluid intake and avoidance of dehydration. Lowering of solute load to the kidneys helps by decreasing free water loss.

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This can be achieved by using hypocaloric formula or by diluting the milk given to the infant. Combinat ion of hyrdochlorothiazide (3 m g / k g / d a y ) and amiloride (0.3 m g / k g / d a y ) has been shown to decrease urine output in these patients by as much as 30-40%. 4 Indomethacin (3

m g / k g / d a y ) , a p r o s t a g l a n d i n synthes i s inhib i tor , increases proximal tubular sodium absorption and has been shown to have synergistic effect to thiazide diuretic in children with NDI?

The presence of intracranial calcification in this case reemphasizes the association of NDI with intracranial calcification. Calcifications in children with NDI have previously been described in basal ganglia, caudate nuclei and f ronta l , par ie ta l and occipi ta l lobes. 6-1~ The pathogenesis of intracranial calcification in NDI is not clear. NDI is associated wi th r ecur ren t ep isodes of hypernatremic dehydrat ion, which causes necrosis of endothelial cells and initiation of dystrophic calcification around the necrosed area. Occurrence of calcification in and a round b lood vessels in NDI s u p p o r t s the hypotheses. 7 Hypematremic dehydration alone, however, cannot explain intracranial calcification, as it has not been reported in children with central DI another condition associated with hypernatremic dehydration. Intracranial calcifications in patients with NDI tend to persist despite adequate t reatment . 9 The associat ion of intracranial calcification with developmental delay emphasizes the need of early diagnosis of NDI prior to the development of this complication.

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