Endocrine Abstracts

Background: Chromosome 22q11.2 deletion syndrome has been reported in about 1 per 347 to 992 living births. Hypocalcemia occurs in up to 80.4% of cases.

Case description: A 28-year-old man, known with autism spectrum disorder (ASD), presented at the emergency department (ED) for limbs muscle cramps. Medical history included chronic myeloid leukemia treated with tyrosine kinase inhibitor (TKI) the last 10 years, gastric bypass and recurrent fractures due to osteoporosis managed by alendronate. The preceding four months, alendronate was switched to zoledronate because of digestive adverse effects. After administration of zoledronate, the patient experienced exacerbation of the muscle stiffness. At the ED, upper limbs spasms (Trousseau’s sign) hindered blood pressure measurement. Shortly after arrival, the patient suddenly developed pulseless electric activity, requiring advanced cardiopulmonary resuscitation, endotracheal intubation and admission to the intensive care unit. Investigations revealed a long QTc at 513 msec, severe hypocalcemia (ionized Ca 0.66 mmol/l [range 1.17-1.33]), normal magnesium, hypophosphatemia (0.49 mmol/l [0.78-1.42]), normal vitamin D and inappropriately low parathyroid hormone (PTH) level (38 ng/l [range 7-70]). Low calcium level was recorded immediately after initiation of TKI ruling out gastric bypass and biphosphonate as primary etiologic factors. Genetic testing was requested based on inappropriately low PTH, asymmetric crying facies, mild epicanthal fold and malar flatness. Deletions of chromosome 22q11.2 spanning catechol-O-methyltransferase (COMT) and T-box transcription factor 1 (TBX1) genes locations were identified. Upon discharge, calcium level improved under oral calcium, magnesium and calcitriol. TKI and biphosphonate were interrupted.

Discussion: In our patient, identification of chromosome 22q11.2 deletion confirmed a constitutional defect in calcium metabolism, which might have been sequentially exacerbated by initiation of TKI, gastric bypass and biphosphonate. Hypocalcemia in DiGeorge syndrome results from hypoparathyroidism and could occurs not only in the neonatal period, but also in adulthood. Other clinical characteristics of the disease encompass cardiac defects, abnormal facies, thymic hypoplasia, cleft palate (CATCH-22). While ascertainment of TBX1 deletion relates to hypoparathyroidism that of COMT gene could be associated to psychiatric defects including ASD and psychosis.

Conclusion: This case highlights the diagnostic complexity of hypocalcemia in a setting of multiple potential etiologic factors. It raises the call to keep in mind that chromosome 22q11.2 deletion syndrome is not that uncommon and can be revealed in adulthood. Specific phenotype, specifically in the setting of hypocalcemia in a patient with inappropriately low PTH, should prompt clinicians to order genetic testing independently of the patient’s age.