Endocrine Abstracts

Marshall-Smith syndrome (MSS) is a congenital disorder characterised by developmental delay, short stature, respiratory difficulties, distinctive facial features, skeletal abnormalities (such as kyphoscoliosis, dysostosis and osteopenia) and delayed neural development, and is due to heterozygous mutations that are clustered in exons 6–10 of the transcription factor nuclear factor I/X (NFIX) gene. These frameshift and splice-site NFIX variants result in t...

Introduction: Hypophosphatasia (HPP) is a very rare systemic musculoskeletal disease characterised by low tissue non-specific alkaline phosphatase (ALP). The prevalence of HPP and its associated morbidity in an adult setting is unclear.Methods: A search for serum ALP results less than 36 IU/l within NHS Greater Glasgow and Clyde between 2017 and 2018 revealed 16 280 results. A further search for patients with two ALP <36 separated by 30 days or more ...

Hypoparathyroidism causes severe hypocalcaemia and defective skeletal metabolism. Treatment with calcium and vitamin D supplementation can cause kidney failure whilst native parathyroid hormone (PTH) requires repeated injections and causes renal impairment paralleling high peak and low trough PTH levels. A long-acting PTH, providing constant physiological levels, is needed. LA-PTH, a hybrid of PTH and PTH related peptide, prolongs cAMP responses via altered receptor mechanisms...

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor that predominantly signals via Gαq/11-mediated pathways to regulate extracellular calcium (Ca2+e) homeostasis. Germline Gα11 inactivating and activating mutations cause familial hypocalciuric hypercalcaemia type-2 (FHH2) and autosomal dominant hypocalcaemia type-2 (ADH2), respectively. To date, four FHH2 and six ADH2 mutations have been reported. To identif...

Familial hypocalciuric hypercalcaemia (FHH) is an inherited disorder of calcium homeostasis, which is caused by germline loss-of-function mutations of the calcium-sensing receptor (CaSR) in ˜70% of cases. We report a 22 year old woman who was referred with asymptomatic hypercalcaemia. Biochemical investigations revealed hypercalcaemia on 3 of 4 occasions with adjusted serum calcium ranging from 2.59–2.80 mmol/l (normal range 2.20–2.60 mmol/l). Parathyroid hormon...

Nephrolithiasis is a major clinical and economic health burden. We performed a genome-wide association study in British and Japanese nephrolithiasis populations and identified twenty nephrolithiasis-associated loci, five of which (DGKD, DGKH, WDR72, GPIC1 and BCR) were predicted to influence calcium-sensing receptor (CaSR) signalling. Gain-of-function CaSR-signalling pathway mutations cause enhanced signalling via intracellular calcium ([Ca2+]...