Endocrine Abstracts

Section 1: Case history: We present the case of a 21-year-old lady known to harbour a homozygous inactivating mutation of the calcium sensing receptor (CaSR) which led to uncontrolled hypercalcaemia in infancy, necessitating emergency total parathyroidectomy. The CaSR plays an important role in calcium homeostasis. Inactivating mutations result in a higher calcium “set-point” and various degrees of hypercalcaemia based on the severity of functional impairment. In the heterozygous state, a single mutation of the gene presents with a milder phenotype, known as familial hypocalciuric hypercalcaemia (FHH). Neonatal severe hyperparathyroidism is a life-threatening condition occurring when both gene copies are mutated. Following parathyroidectomy the patient developed hypoparathyroidism, requiring treatment with 1-alfacalcidol and sandocal. Aged 21 she became pregnant. Paternal testing showed normal serum calcium, hence the fetus was expected to inherit a maternal mutated copy of the gene and a paternal wild-type copy (and hence be heterozygous for the CaSR mutation). This genotype would result in the fetus having a higher serum calcium, albeit to a much lesser degree than that seen in the homozygous state.

Section 2: Investigations: Following biochemical testing of the maternal grandparents, the fetus’ anticipated corrected serum calcium concentration was predicted to be around 2.8 mmol/l. Thus, a maternal serum calcium concentration less than 2.8 mmol/l would likely be perceived by the fetus as being ‘low’ and subsequently result in fetal secondary hyperparathyroidism. Following birth, this would put the baby at risk of neonatal hypercalcaemia.

Section 3: Results/treatment: Serial growth scans showed normal fetal growth and skeletal architecture. Maternal requirement for calcium increased as pregnancy progressed and extracellular fluid volume expanded. The baby was born by vaginal delivery following induction of labour at 39+4 weeks’ gestation, weighing 2.6 kg. At birth, the neonate’s corrected serum calcium concentration was 2.87 mmol/l (ref. 2.2–2.6), with a normal phosphate. On day 4, corrected calcium was 2.81 mmol/l, PTH 1.6 pmol/l (ref 1.6–6.9), urine calcium 1.8 mmol/l, urine creatinine 1.2 mmol/l. Corrected calcium aged 4 months was 2.73 mmol/l, PTH 4 pmol/l, urine calcium 0.5 mmol/l, urine creatinine 0.4 mmol/l. Genetic testing on the baby identified a heterozygous mutation of the CaSR, consistent with FHH.

Section 4: Conclusions/points for discussion: We hereby discuss the changing physiology and management of hypocalcaemia in a pregnant patient harbouring a homozygous CaSR mutation and concerns arising for both mother and fetus.