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 12-year-old boy presented with a new onset generalized tonic-clonic seizure. He is the first child of a phenotypically normal mother. The patient was born at term after an uneventful pregnancy by an uncomplicated caesarean section with low birth weight of 2,900g (10–25th percentile). At 8 months the child underwent surgical repair of a cleft palate and at age 2 years had two episodes of febrile convulsion. He had a learning disability in his school-aged years. On family history, his father had a prominent forehead, small down-turned mouth, micrognathia, and nasal voice (). He had not undergone any prior specific evaluation, but seemed to have normal intelligence without any neuropsychiatric symptoms including a seizure history.\nPhysical examination revealed prominent forehead, small down-turned mouth, micrognathia (), and repaired cleft palate with not well formed uvula (). His height was 146 cm (25–50th percentile) and weight was 38.5 kg (25–50th percentile). Chvostek’s and Trousseau’s signs were negative. He had mild mental retardation with an intelligence quotient (IQ) of 68 on the Korean version of Wechsler Intelligence Scale for Children (K-WISC).\nThe electrocardiogram (ECG) was abnormal due to a prolonged corrected QT interval and the chest radiograph failed to show a thymus shadowing. Computed tomography (CT) of the heart revealed right aortic arch (), and CT of the brain showed multiple calcifications in the bilateral basal ganglia and both frontal white matters (). The electroencephalogram (EEG) revealed generalized intermittent slow waves without any epileptiform discharges.\nLaboratory tests showed hypocalcemia (calcium 6.5 mg/dL, ionized calcium 2.8 mg/dL), hyperphosphatemia (9.1 mg/dL) and normal level of magnesium (1.8 mg/dL). Parathyroid hormone (PTH) was decreased to 4.76 pg/mL (reference range 15–65 pg/mL) and 25-vitamin D3 was decreased to 13.6 ng/mL (reference range 30–60 ng/mL). Peripheral blood count, hepatic, renal and thyroid function tests were all normal except thrombocytopenia (144,000/μL). Immunological studies showed normal levels of Immunoglobulins but T cell subpopulation analysis was abnormal. T lymphocyte was decreased to 42.8 %/μL (reference range 52–78%/μL), CD4/CD8 T cell ratio was decreased to 0.79 (reference range 0.8–3.0).\nFluorescent in situ hybridization (FISH) analysis was performed using peripheral blood and chromosomal study was carried out using DiGeorge/VCFS TUPLE1 region probe (22q11.2) with an ARSA control probe (22q13) which confirmed a 22q11.2 deletion. His father revealed the same chromosomal abnormality, which suggests paternal inheritance in this case.\nThe patient was treated with calcium citrate and calcitriol. He remained asymptomatic with normalization of his serum calcium level with medications.