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 26-year-old Thai man without underlying disease came to emergency unit because of carpopedal spasm for 4 hours. He also reported numbness and tingling at perioral area and muscle cramps in both legs. The patient's history of birth and development was normal, and he had been previously healthy. He had no history of recurrent infection or cardiac disease. He had attended 6 years of elementary school, and is working as an unskilled laborer. He did not drink alcohol or use illicit drugs. There was unremarkable family history.\nOn examination, the patient was alert. His height was 153 cm (<3rd centile) and his weight was 65 kg (body mass index =27.77 kg/m2). His blood pressure was 100/60 mm Hg and pulse was 80 beats per minute. He had bilaterally carpopedal spasm and positive Chvostek's sign. Cardiac, chest, and abdominal examinations were unremarkable. He had no subcapsular cataract. Laboratory investigations showed hypocalcemia with calcium level of 1.5 mmol/L (normal range, 2.2–2.53 mmol/L), ionized calcium level of 0.7 mmol/L (normal range, 1.09–1.3 mmol/L), and hyperphosphatemia with phosphate level of 1.68 mmol/L (normal range, 1.07–1.49 mmol/L). Serum PTH level of 24.2 pg/mL (normal range, 15–65 pg/mL) was inappropriately normal during severe hypocalcemia. Serum magnesium and creatinine level were normal. Complete blood count and other biochemistry tests were also within normal limit. According to laboratory findings, hypocalcemia secondary to hypoparathyroidism was diagnosed. His electrocardiogram revealed prolonged QT interval with corrected QT interval of 473 msec (normal < 450 msec in male) and no ST-T change. Intravenous infusion of 10% calcium gluconate with bolus dose and continuous rate of 1 mg of elemental calcium/kg/hr was administered with concomitant oral calcium and vitamin D analogues.\nTo search for the cause of hypoparathyroidism, he had no history of neck surgery or irradiation. Morning serum cortisol level, thyroid function test, and hemoglobin A1C were normal, polyglandular autoimmune syndrome is less likely. At first presentation, we did not recognize any dysmorphic features. However, minor facial abnormalities were detected by meticulous examination. He had a prominent forehead, hypertelorism, hooded eyelids, ear microtia, low set ear, thick and overfolded ear helix, left external auditory canal stenosis, broad nasal bridge, and prominent lips (). His intelligence quotient or IQ by Wechscler Adult Intelligence Scale was 69, which categorized as mild mental retardation. Primary hypoparathyroidism along with dysmorphic face and mild mental retardation lead to suspicion of chromosome 22q11.2 deletion syndrome in this patient. Conventional chromosome analysis using the standard G band procedure showed a normal male karyotype. Subsequently, Array Comparative Genomic Hybridization (CGH) analysis was performed using Agilent custom-designed 44 K oligonucleotide array. The array contains more than 41,000 oligonucleotide probes and has both genome-wide coverage and dense coverage in regions of known microdeletion/duplication syndromes, subtelomeric and pericentromeric regions (Genzyme Genetics, Monrovia, CA). The CGH array showed a copy loss of 192 oligonucleotide probes in the region of 22q11.2 (genomic coordinates 17289032–19687983), with an estimated size of approximately 2.40–3.14 Mb at 22q11.21 region. The 22q11.2 deletion was confirmed by a fluorescent in situ hybridization (FISH), using the HIRA probe (Abbott Molecular). The deleted region contains approximately 34 OMIM genes. Further investigations included transthoracic echocardiography, renal ultrasonography, and dental examination were all normal. Audiography showed bilateral conductive hearing loss. CT brain found bilateral basal ganglion calcification. Finally, he was diagnosed with chromosome 22q11.2 deletion syndrome (microdeletion). Genetic counseling was informed to him and his family. He was discharged from the hospital with 1,000 mg elemental calcium as calcium carbonate and 0.25 μg alfacalcidiol twice daily. The serum calcium level was maintained in lower normal range to prevent hypercalciuria. During subsequent follow-up, the patient did not have any recurrence of hypocalcemic symptom.