An 11-year-old girl visited our Emergency Department with fever, cough, abdominal pain and vomiting. Hypocalcemia (serum calcium, 5.0 mg/dL; ionized calcium, 0.74 mM) was noted on laboratory analysis, with normal albumin (4.3 mg/dL), and upper normal limit level of phosphorus (5.6 mg/dL).\nShe was born with 3,040 g of body weight at 37 weeks of pregnancy at our hospital and was the second child of phenotypically normal Korean parents. Imperforate anus with rectovestibular fistula and partial cleft palate were found at birth. Atrial septal defect (ASD, 3.5-mm width) was diagnosed on echocardiography performed on the first day of life. However, the karyotyping revealed normal chromosomal pattern by GTG banding. Descending colostomy was performed on the first day of life and followed by colostomy repair at 9 months of age. Pena operation (posterior sagittal anorectoplasty) was performed at 4 months of age and transposition anoplasty was done at 7 months of age. Palatoplasty for cleft palate was performed at 14 months of age, and again at 9 years of age, velopharyngeal insufficiency was surgically corrected by superiorly based pharyngeal flap with lateral port control. Echocardiography at 20 months of age showed no intracardiac anomaly, suggesting spontaneous closure of previously observed ASD. She had suffered from frequent respiratory tract infections with otitis media and chronic constipation, but there was no history of severe systemic infection. Her developmental milestones were delayed, and she was diagnosed for mild intellectual disability at 8 years of age (Intelligence quotient 57 on Korean Wechsler intelligence scale for children). She was attending a public school without specific behavioral problems, although her academic performance was poor.\nOn the third day of life, her calcium (9.2 mg/dL), phosphorus (4.5 mg/dL), and ionized calcium (1.05 mM/L) levels were normal. Her calcium level was also normal on preoperative screening before surgery at 4, 7, and 9 months of age (10.5, 10.8, and 10.6 mg/dL, respectively). Her calcium level was in low normal range on laboratory studies at 20 months and 7 years of age (9.1 and 8.9 mg/dL, respectively). The parents denied any history of hypocalcemic symptoms during her infancy or childhood.\nHer facial features appeared mildly dysmorphic, with hypertelorism, short philtrum and small down-turned mouth. Hypernasal speech was not observed. At the time of hypocalcemia onset at 11 years of age, her height was 141 cm (25th percentile) with weight 31 kg (10th–25th percentile). Her midparental height was 157 cm (10th–25th percentile). Her wrist X-ray showed bone age of 12 years without any evidence of rickets. Serum magnesium level was normal (1.63 mg/dL). The parathyroid hormone (PTH) level was inappropriately low (10.8 pg/mL; reference rage, 15–65 pg/mL) considering her plasma calcium level, suggesting hypocalcemia due to hypoparathyroidism. Serum 25(OH)D level was also decreased (11.4 ng/mL; reference range, 30–100 mg/mL). Her thyroid function was normal (thyroid-stimulating hormone, 0.28 uIU/mL; free T4, 1.68 pg/mL).\nIntravenous calcium (calcium gluconate, 100 mg/kg) was given during the first 3 days after admission, followed by oral calcium (calcium lactate, 300 mg/kg/day). Vitamin D (calcitriol, 0.75 µg/day) treatment was started on the 2nd hospital day. She was discharged on the 6th hospital day when her calcium level was 6.5 mg/dL. Her calcium level increased to 8.3 mg/dL on follow-up visit at 1 week after discharge, and her PTH level was still low (9.0 pg/mL). Although 25(OH)D level has been normalized (25.5 and 30.5 ng/mL after 2 months and 3 months, respectively) after treatment, daily administration of calcium (calcium carbonate, 62.5 mg/kg/day) and calcitriol (0.5 µg/day) was required to maintain normocalcemia (serum calcium 9.2 and 8.3 mg/dL after 2 and 3 months, respectively).\n22q11DS was suspected based on her history of velopharyngeal insufficiency and mental retardation, and fluorescence in situ hybridization analysis confirmed a deletion of chromosome 22q11.2 ().
A 44-year-old woman was admitted to hospital for further evaluation of recurrent episodes of syncope with a long QT-interval associated with hypocalcaemia. The patient had experienced epileptic seizures as a child, but no treatment had been required. No further epileptic events were reported after puberty. Otherwise, past medical and surgical history was unremarkable. The patient denied taking recreational drugs or consuming alcohol. There was no history of inherited diseases among relatives.\nThe patient experienced her first syncope episode in 2014 while she was doing housework; this occurred without any prodrome or signs of vasovagal reaction (i.e. fainting, nausea, sweating, blurred vision, tingling of lips or fingertips). The fall caused by the syncope led to a fracture of the atlas arch and she was admitted to the hospital. On admission, vital parameters were oxygen saturation 98%, blood pressure 124/65 mmHg, heart rate 80/min; there was no cyanosis, oedema, or bibasilar rales in the lungs. She was awake and oriented, with no focal neural deficits. Cranial computed tomography (CCT) ruled out cerebral pathologies. The electrocardiogram (ECG) on admission showed a prolonged QT interval with corrected QT (QTc) of 520 ms, associated with a hypocalcaemia (calcium level 1.4 mmol/L) (). Echocardiography showed apical hypokinesia and coronary angiography revealed normal coronary arteries. Cardiac magnetic resonance tomography ruled out structural heart disease and there were no signs of myocarditis. Serial ECG showed a normal QTc when serum calcium levels were within the normal range. No significant arrhythmias were documented on 7-day-Holter monitoring.\nHypocalcaemia was interpreted as part of a newly diagnosed primary hypoparathyroidism, and substitution therapy with vitamin D (1000 U/day) and calcium (500 mg twice daily) was started. However, the patient admitted to not having taken medication shortly before a second syncope event that occurred suddenly at home in 2019, which resulted in fracture to the jaw and hand. Physical and emotional stress at that time were denied. Physical examination including neurological assessment was unremarkable. CCT revealed neither intracranial bleeding nor an ischaemic event. Levetiracetam 500 mg twice a day was prescribed by neurologist due to an increased epileptic activity on electroencephalography. In the absence of other possible causes, this event was assumed to also be related to hypocalcaemia.\nECG on admission to our hospital () showed no significant conduction disorders and no repolarization abnormalities. Telemonitoring was unremarkable except for a single 3-min episode of a self-terminated supraventricular tachycardia with sudden onset and a heart rate of 140 beats/min without any haemodynamic compromise. Laboratory tests showed hypocalcaemia (1.76 mmol/L) due to reduced parathormone production; all other electrolytes were within normal ranges; haemoglobin was 12 mg/dL. High-sensitivity troponin was not elevated. Although it had not previously been documented, we noted mild facial dysmorphia (i.e. prominent nose with large tip and hypoplastic nares, small dysmorphic ears). The combination of transient hypocalcaemia with subtle facial characteristics were thought to be indicative of one of the velocardiofacial syndromes, namely DiGeorge syndrome. Subsequent genetic test showed a microdeletion in 22q11.2, confirming the diagnosis ().\nThere are two possible mechanisms of hypocalcaemia inducing a TLOC: arrhythmogenic syncope or seizure. Because our patient showed prolonged QTc immediately after the first episode, we assumed that she had experienced an arrhythmogenic syncope, and that this was caused by a hypocalcaemia-induced long QT syndrome. Therefore, it was decided to implant an event recorder for the detection of arrhythmic events. Substitution therapy with calcium carbonate 500 mg twice daily and vitamin D 1000 U/day was initiated. The calcium level was monitored every 3 months and dosages adjusted by an endocrinologist as required. The patient was also examined by neurologist. Although we made a strong recommendation for psychiatric evaluation, the patient declined. No further organ systems were affected. No recent syncope was reported during 12 months of follow-up and there were no arrhythmic events stored by the event-recorder.