A 14 month previously healthy girl was brought to our institute with history of not able to sit, loss of neck control and inability to recognize and interact with mother for last 3 months, and vomiting for last 3 days. There was no history of fever, loose motions, convulsions, trauma, toxin ingestion or contact with tuberculosis. She was the only child of her parents born to non consanguineous couple. Antenatal, perinatal, neonatal, past and family histories were unremarkable. Her developmental milestones were normal till the age of 11 months.
On examination, she was lethargic, interacted poorly with mother and surroundings. She was hypotonic with frog-legged posture though spontaneous limb movements were present. Her vital parameters and hydration were normal. Her weight was 7.0 kg (-2.5 Z score), length 74 cm (-1 Z score), and head circumference 43 cm (-1.8 Z score). She had head lag on pull to sit, axial and appendicular hypotonia, power of all 4 limbs was at least grade III, deep tendon reflexes were non elicitable and bilateral plantar was down going. Rest of the systemic examination was normal. Work up for encephalopathy, neuroregression and hypotonia was done, suspecting inborn errors of metabolism.
Her complete blood count, renal and liver profiles, creatine kinase, thyroid function test (TFT), serum vitamin B12 levels and blood gas analysis were normal. Screening for amino acid disorders, organic acidemias and fatty acid oxidation defects on dried blood sample by tandem mass spectrometry was normal. Electrocardiography (ECG) was normal with QTc 0.32 second. Ultrasound abdomen kidney ureter bladder, x ray abdomen (for nephrocalcinosis), echocardiography and magnetic resonance imaging (MRI) of brain was normal. Hearing assessment was normal. The only abnormality detected was high serum and ionic calcium levels of 15.7 mg/dL (normal 9.0 to 11.0 mg/dL) and 1.9 mmol/L (normal 1.22 to 1.37 mmol/L) respectively. Serum phosphorus and magnesium levels were normal.
Further work up for hypercalcemia revealed serum 25-OH vitamin D level in toxic range and low serum intact parathormone (PTH) level suggestive of exogenous vitamin D intoxication (Table 1).
On probing, parents revealed that baby had received 4 sachets of vitamin D orally, each of 60,000 IU (total 2.4 lakh IU) at an outside hospital and was not on any prolonged supplementation. Fluorescent in situ hybridization (FISH) targeted to the 7q11.23 region for Williams-Beuren syndrome (WBS) was done as dysmorphism in WBS is not easily appreciated in infancy and vitamin D intoxication in our case occurred at therapeutic doses and was negative; although WBS has global developmental delay rather than neuroregression and 80-90% cases have cardiovascular manifestations. Diagnosis of hypercalcemia secondary to vitamin D intoxication was made.
Child was treated with intravenous bolus of normal saline, followed by continued oral and/ or intravenous hydration at 1.5 to 2 times maintenance and intravenous furosemide 1.5 mg/kg/dose every 8 hours. Fluid volume status, electrolytes (including serum calcium) and ECG were monitored. During treatment baby developed hypokalemia which was managed as per protocol. With improvement of sensorium, baby was started on breast feeding and feeding via orogastric tube along with intravenous fluids. Serum calcium decreased but remained elevated after 8 days, so pamidronate was planned but could not be given due to non-availability (Figure 1). Oral prednisolone 2 mg/kg/day was started. Serum calcium was near normal, and baby became alert, playful, started recognizing mother, regained social smile, started holding neck, and was sitting with support after 2 weeks of therapy, and was discharged with the plan to taper and stop prednisolone on follow up.