Endocrine Abstracts

Alkaline phosphatase (ALP) was discovered by Robert Robison, PhD in London in 1923. In New York in 1932, he added to his hypothesis that ALP functioned in skeletal calcification by liberating inorganic phosphate (Pi) for hydroxyapatite crystal formation, perhaps from a hexosephosphoric ester, some unknown factor also conditioning this process. In 1948 in Toronto, Canada, ‘hypophosphatasia’ (HPP) was coined by John C. Rathbun, MD to describe a unique rickets without r...

Familial hypocalciuric hypercalcaemia type-3 (FHH3) is caused by loss-of-function mutations of the sigma subunit of adaptor protein-2 (AP2), a ubiquitously expressed heterotetrameric protein with a fundamental role in endocytosis of transmembrane proteins. FHH3-associated AP2σ mutations impair internalisation of calcium-sensing receptor (CaSR) giving rise to FHH. CaSR predominantly signals via Gαq/11 leading to intracellular calcium release, and activation...

The calcium-sensing receptor (CaSR) belongs to family C of G-protein coupled receptors (GPCRs) that bind glutamate, GABA, taste molecules and pheromones. Loss-of-function mutations of the CASR gene located on chromosome 3q21–24, cause familial benign hypocalciuric hypercalcaemia type 1 (FBHH1). The genes causing FBHH2 and FBHH3, whose chromosomal locations are on 19p and 19q13.3, respectively, remain unknown. FBHH3, sometimes called the Oklahoma variant (FBHHO...

In XLH, high circulating FGF23 causes hypophosphatemia, rickets, and short stature. In our Phase 2 study, 52 XLH children (ages 5–12 years, ≤Tanner 2) were randomized to receive KRN23 subcutaneously biweekly (Q2W) or monthly (Q4W). Serum phosphate (Pi) was measured biweekly. KRN23 dose was titrated (maximum 2 mg/kg) targeting age-appropriate serum Pi concentrations.The first 36 subjects had a mean 6.6 years of standard-of-care treatment before...

Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder characterized by lifelong elevation of serum calcium concentrations with inappropriately low urinary calcium excretion. Three types referred to as FHH1, FHH2 and FHH3 and located on chromosomes 3q21.1, 19p and 19q13.3, respectively, have been reported. FHH1, caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), accounts for >65% of FHH patients. To identify the gen...

Familial hypocalciuric hypercalcaemia (FHH) comprises three types: FHH1, FHH2, and FHH3, which are due to mutations of the calcium-sensing receptor (CaSR), G-protein α 11 subunit (Gα11), and adaptor protein-2 sigma subunit (AP2σ), respectively. The aims of this study were: to assess for genotype–phenotype correlations among the three reported FHH3-causing AP2σ mutations, which all involve the Arg15 residue, and comprise Arg15Cys, Arg15His, and Arg15Leu...