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Neonatal hyperparathyroidism is a rare disease caused by a homozygous inactivating mutation in the calcium sensing receptor gene. It presents early in life with life threatening manifestations of hypercalcemia, if left untreated the condition may be lethal. This is the first case series reported from Sudan. Three Sudanese siblings presented with severe symptoms of hypercalcemia in the form of polyuria, failure to thrive and multiple bone fractures. Serum calcium and parathyroid hormone levels were very high with low phosphate and normal alkaline phosphatase levels. Ultrasonography and sestamibi scan were normal and did not assist in diagnosing their condition. Medical management was a great challenge due to unavailability of medications such as parentral bisphosphonates and calcimimetics. Parathyroidectomy was inevitable. Tissue biopsies revealed parathyroid hyperplasia and no adenoma. Gene sequencing revealed a homozygous missense mutation: c 2038 C T p (Arg680Cys) in two siblings, both parents were heterozygous for the same missense mutation. Our report reflects the challenges in diagnosis and management of neonatal hyperparathyroidism in resource limited countries. We also highlight the importance of genetic testing in the diagnosis and management of such cases in countries with high rates of consanguineous marriage.
Case 1 {(1V/12), Figure 1}: a 7-month-old female presented with multiple bone fractures and was accidentally found to have hypercalcemia on routine investigations. She had a history of NICU admission for what was thought to be neonatal sepsis because of poor feeding and floppiness, chronic constipation, and failure to thrive but no history of urinary stones. Her birth was 2.8 kg. There were no dysmorphic features and her weight at presentation was 5 kg (-2.6 standard deviation (SD) below the mean for her age and sex). Parents are healthy first-degree cousins. The daughter of her maternal cousin was diagnosed with hyperparathyroidism in infancy which required parathyroidectomy. The biochemical, radiological, and histopathological findings are shown in Table 1. Her mother´s calcium level was 11.3 mg/dl (2.83 mmol/l), father´s level was 9.1 mg/dl (2.27 mmol/l). Vitamin D3 was not measured for the parents. She only showed a partial response to medical treatment of hypercalcemia, in the form of intravenous saline with furosemide 2 mg/kg/dose TDS, bisphosphonates in the form of oral alendronate 10 mg/day and calcitonin 4 IU/kg given subcutaneously every 6 hours. The lowest calcium level achieved with medical treatment was 17 mg/dl. Surgical intervention was inevitable and included total parathyroidectomy through bilateral neck incision and removal of the four parathyroid glands with re-implantation of one gland in the sternocleidomastoid muscle. Following surgery, she remained symptomatic with persistently high levels of calcium and PTH. The condition was not responsive to same medical treatment mentioned and required a second surgery to remove any remaining parathyroid tissue 8 weeks following the first surgery. Her calcium levels normalized immediately following the second surgery and after which she remained asymptomatic with normal calcium levels without any treatment. She managed to catch up normal growth for her age by the age of 36 months. family pedigree biochemical, radiological and histopathological findings in case one and two PTH: parathyroid hormone; UCCR: urinary calcium creatinine ratio Case 2 {(1V/13),(Figure 1)} a younger male sibling, presented at the age of 8 months with a history of chronic constipation, abdominal pain, polyuria, failure to thrive, and floppiness since birth. a younger male sibling, presented at the age of 8 months with a history of chronic constipation, abdominal pain, polyuria, failure to thrive, and floppiness since birth. He had no history of bone fractures nor urinary stones. There were no dysmorphic features and his weight was 6 kg (-3.5 SD). His biochemical and radiological findings are shown in Table 1. Hypercalcemia was resistant to available medical treatment in the form of intravenous saline and furosemide, oral bisphosphonates, and calcitonin. Surgical intervention was required and removal of all four parathyroid glands with reimplantation of the fourth one in the sternocleidomastoid muscle was done. Immediately following surgery, he developed hypocalcemia and required intravenous calcium then was shifted to oral calcium supplementations, 40 mg/kg/day for 6 weeks after which his calcium levels normalized. There after 6 weeks from his surgery he remained asymptomatic with normal calcium levels and required no further treatment. He managed to catch up to normal growth for his age at 30 months. Case 3 {(1V/14), (Figure 1)}: the younger sibling presented post-delivery with severe symptoms of hypercalcemia, bone fractures and respiratory distress that required ventilatory support. PTH and calcium levels were high. Management required parathyroidectomy. Further medical data was difficult to access as this patient was born abroad in Saudi Arabia (Figure 1).
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