Refractory Yet Transient Neonatal Hypocalcemia Due to Hitherto Undiagnosed Asymptomatic Maternal Hyperparathyroidism: A Case Report

Hypocalcemia is one of the common causes of neonatal seizures and can result in significant morbidity. Among the multitude of etiologies, hypoparathyroidism as a consequence of maternal hyperparathyroidism is an uncommon one. We describe a neonate who presented with hypocalcemic seizures with relative hypoparathyroidism that unmasked a previously undiagnosed and asymptomatic maternal hyperparathyroidism, and explore the difficulties encountered in the management. Despite initial recalcitrance of hypocalcemia to therapy, parathyroid suppression was transient and recovered completely in few months.

Bacteremia in a Newborn with Hypocalcemic Seizures and Vitamin D Deficiency

Infants with neonatal hypocalcemia often present with seizures, and neonatal hypocalcemia can be due to parathyroid (PTH) insufficiency or resistance. Causes of hypocalcemia with PTH elevation include increased phosphate load, vitamin D deficiency (VDD) or defects in metabolism, renal dysfunction, hypomagnesemia, genetic mutations resulting in end-organ resistance to PTH, or critical illness. Hypocalcemia has also been shown to be associated with Gram-negative bacteremia and sepsis in adults. We present the case of a full-term, formula-fed newborn presenting with late-onset hypocalcemic seizures and VDD in the setting of Klebsiella pneumoniae bacteremia. This case highlights that newborns presenting with hypocalcemic seizures should undergo a workup for sepsis.

Late-Onset Neonatal Hypocalcemia Due to Transient Hypoparathyroidism in Infant of Mother With COVID-19 at Delivery

Introduction: Neonatal hypocalcemia is an uncommon condition but clinical presentation can include severe manifestations such as neuromuscular irritability, tetany, seizure or cardiac conduction abnormalities that require prompt intervention to normalize calcium levels. To our knowledge there have been no reports of neonatal hypocalcemia following maternal SARS-CoV2 infection at the time of birth. Here we report a case of transient late-onset neonatal hypocalcemia complicated by maternal SARS-CoV-2 infection at the time of delivery. Clinical Case: A 13-day old full-term appropriate for gestational age female was born to an asymptomatic mother who tested positive for SARS-CoV2 at the time of delivery. Caretakers noticed minor twitching movements in the first few days of life that were progressively worsening. Initial ionized calcium was 0.6 mmol/L, and labs at time of transfer to our hospital were notable for total calcium of 5.5mg/dL(n 8.9–9.9), and ionized calcium of 0.67mmol/L (n 1.12–1.37 mmol/L). Calcium levels improved after she received IV calcium boluses and was started on continuous IV calcium infusion. Initial phosphorus was 8.3 mg/dL (n 3.2–7.4 mg/dL) and magnesium was 1.2 mg/dL (n 1.5–2.2 mg/dL), while intact PTH was inappropriately low at 12.2 pg/mL (n 10–65 pg/mL), and urine calcium to urine creatinine ratio was below the limits of assay detection (n <0.86), consistent with a diagnosis of neonatal hypoparathyroidism. The 25-hydroxy vitamin D was 11.1 ng/mL (n 30–100 ng/mL), which may have also been a contributing factor. She had no dysmorphic features on examination concerning for 22q deletion syndrome, and tested negative for SARS-CoV2. Chromosomal microarray did not reveal clinically relevant copy number alterations or areas of homozygosity. Calcium stabilized on enteral calcium carbonate, calcitriol, and cholecalciferol, and she was weaned off of all supplementation. Prior to discharge PTH recovered to 36.9 pg/ml with a calcium of 9.9 mg/dL, phosphorus 7.7 mg/dL, normal magnesium and 25-hydroxy vitamin D (31.3 ng/ml). She was discharged on Similac PM 60/40 formula to reduce her dietary phosphorus content, and 400 IU of cholecalciferol. Conclusions: Hypocalcemia in patients with severe COVID-19 is being increasingly reported. There is minimal data on the effect of perinatal SARS-CoV2 infections on neonatal health. While this report does not establish causation, expanding awareness of neonatal abnormalities following maternal SARS-CoV2 infection at delivery will help to recognize causal associations and improve patient care.

Neonatal Hypocalcemia in the Infant of a Diabetic Mother

Neonatal hypocalcemia (NHC) is one of the most common disorders of calcium metabolism in infants admitted to the NICU. Presentation can range from asymptomatic to generalized seizures or tetany. In this case study, an infant with NHC is presented along with an overview of the pathophysiology, prevalence, diagnosis, and management of NHC for neonatal clinicians.

Neonatal hypocalcemic Seizures: About a 41-Day-Old Infant

Neonatal crises have several etiologies. Hypovitaminosis D and hypocalcemia are the most common cause of childhood seizures, but their frequency has been reduced due to vitamin D supplementation and infant formula. Most hypocalcemic crises have an underlying endocrinological origin rather than a deficit in intake. We describe the case of a 41-day-old infant admitted for neonatal seizures for hypocalcemia. Although symptoms and concentrations of calcium and parathyroid hormone (PTH) levels favored isolated congenital hyperparathyroidism after eliminating other differential diagnoses. The course of the disease was favorable with intravenous (IV) calcium gluconate 10%, then orally alfacalcidol and vitd2. The case is presented with a brief review of the pathophysiology, differential diagnosis and treatment of neonatal hypocalcemia.

Neonatal Hypocalcemic Seizures in Offspring of a Mother With Familial Hypocalciuric Hypercalcemia Type 1 (FHH1)

Context Familial hypocalciuric hypercalcemia type 1 (FHH1) is caused by loss-of-function mutations of the calcium-sensing receptor (CaSR) and is considered a benign condition associated with mild-to-moderate hypercalcemia. However, the children of parents with FHH1 can develop a variety of disorders of calcium homeostasis in infancy. Objective The objective of this work is to characterize the range of calcitropic phenotypes in the children of a mother with FHH1. Methods A 3-generation FHH kindred was assessed by clinical, biochemical, and mutational analysis following informed consent. Results The FHH kindred comprised a hypercalcemic man and his daughter who had hypercalcemia and hypocalciuria, and her 4 children, 2 of whom had asymptomatic hypercalcemia, 1 was normocalcemic, and 1 suffered from transient neonatal hypocalcemia and seizures. The hypocalcemic infant had a serum calcium of 1.57 mmol/L (6.28 mg/dL); normal, 2.0 to 2.8 mmol/L (8.0-11.2 mg/dL) and parathyroid hormone of 2.2 pmol/L; normal 1.0 to 9.3 pmol/L, and required treatment with intravenous calcium gluconate infusions. A novel heterozygous p.Ser448Pro CaSR variant was identified in the hypercalcemic individuals, but not the children with hypocalcemia or normocalcemia. Three-dimensional modeling predicted the p.Ser448Pro variant to disrupt a hydrogen bond interaction within the CaSR extracellular domain. The variant Pro448 CaSR, when expressed in HEK293 cells, significantly impaired CaSR-mediated intracellular calcium mobilization and mitogen-activated protein kinase responses following stimulation with extracellular calcium, thereby demonstrating it to represent a loss-of-function mutation. Conclusions Thus, children of a mother with FHH1 can develop hypercalcemia or transient neonatal hypocalcemia, depending on the underlying inherited CaSR mutation, and require investigations for serum calcium and CaSR mutations in early childhood.