ESPE Abstracts

Introduction: Heterozygous inactivating mutations of the calcium-sensing receptor encoding gene (CASR) cause autosomal dominant familial hypocalciuric hypercalcemia (FHH), whereas mutations that inactivate both alleles cause neonatal severe hyperparathyroidism (NSHPT), a rare and potentially fatal disease. We present the clinical and genetic characterization of a Portuguese family with FHH/NSHPT as well as the long-term follow-up of the proband.

Case Report: A female 16-day-old newborn was admitted to neonatal intensive care due to progressive hypotonia, feeding refusal, and dehydration. Serum calcium and PTH levels were markedly increased. Radiological evaluation revealed osteopenia and several fractures. Total parathyroidectomy with reimplantation of ¼ of one gland was performed. Se has been regularly follow-up since then. At 15-year-old she is clinically well, growing normally (height -0.53 Standard Deviation Score), has normal calcium levels and detectable parathormone values, under calcium and α-calcidiol treatment. CASR gene sequencing revealed a germline homozygous nonsense mutation (c.679C>T p.Arg227Ter), which is predicted to encode a severely truncated receptor. The proband’s parents and grandfathers were asymptomatic, heterozygous carriers of the same mutation.

Conclusions: NSHPT complexity requires a multidisciplinary approach to minimize morbidity. In the present case, total parathyroidectomy with reimplantation was needed to control hypercalcaemia. After a challenging admission to control calcium levels the proband is currently clinically well. Identification of a CASR mutation allowed family genetic counseling.