Endocrine Abstracts

Osteoporosis and associated fractures are the most common and debilitating complication of glucocorticoid use. The use of alternative anti-inflammatory agents without the catabolic and deleterious skeletal side-effects of glucocorticoids is needed. Dehydroepiandrosterone (DHEA) may have immunomodulatory as well as positive effects on bone. To further our understanding of the mechanisms of action of DHEA, as a steroid-sparing agent, we investigated and compared the effects of D...

SEMDs are a heterogeneous group of skeletal disorders characterised by defective growth and modelling of the spine and long bones. Genetic defects in two inherited SEMDs have been identified and these involve abnormalities of the collagen type II gene located on chromosome 12q12-q13.2, and an ATP sulfurylase/APS kinase gene located on 10q23-34. These are not the cause of the Missouri variant (SEMDMO), which occurs as an autosomal dominant trait in a unique four-gene...

X-linked recessive hypoparathyroidism (XLHPT), due to congenital parathyroid agenesis, has been reported in two related kindreds from Missouri, USA. Affected individuals, who are males, suffer from epilepsy due to hypocalcaemia during infancy, whilst the females are normocalcaemic. Studies have mapped XLHPT to chromosome Xq27 and defined a 1.5 Mbp interval flanked centromerically by Factor IX and telomerically by DXS984. DNA sequence analysis of 4 candidate genes (proto-dbl, A...

(This poster is based on OC3)...

Hereditary multiple exostosis (HME) is an autosomal dominant disorder characterised by the development of benign cartilage-capped tumours, located at the juxtaepiphyseal regions of long bones. Patients suffer from short stature and skeletal deformities and may occasionally develop chondrosarcomas or osteosarcomas.HME is a genetically heterogeneous disorder and three loci referred to as EXT1, EXT2 and EXT3 have been mapped to chromosomes 8q24.1, 11p11-12...

Background: Growth monitoring identifies treatable conditions in apparently healthy children and prevents inappropriate referrals. Systematic growth monitoring is not currently a UK priority and growth disorders are frequently diagnosed late.Objectives: Develop and test the accuracy of a smartphone app which enables families to measure a child’s height at home as a cost-effective alternative to primary care growth monitoring.M...

Dent’s disease, due to mutations in the chloride/proton antiporter, CLC-5, represents one form of familial hypophosphataemic rickets. Dent’s disease patients also have: low-molecular-weight-proteinuria; hypercalciuria with nephrolithiasis and renal failure; and urinary loss of parathyroid hormone and vitamin D-binding protein, due to defective receptor-mediated endocytosis within the renal proximal tubule. However, there is variability in these clinical phenotypes su...

Receptor-mediated endocytosis (RME), involving megalin and cubilin, mediates renal proximal-tubular reabsorption of glucose, proteins and hormones including insulin, parathyroid-hormone and vitamin D. RME disruption occurs in Dent’s disease patients with mutations of the chloride/proton antiporter, CLC-5, who suffer from low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis and renal failure. To further investigate the RME role of CLC-5 we established conditio...

Activating mutations of the calcium sensing receptor (CaSR) result in autosomal dominant hypocalcaemia with hypercalciuria (ADHH), in which patients may also suffer from polyuria, polydipsia, nephrocalcinosis, renal impairment, and ectopic calcification. A mouse model, Nuf, with an activating Leu723Gln CaSR mutation has been reported to develop the features of ADHH as well as cataracts that consist of dot nuclear opacities, which have not been described in ADHH patients...

Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of tumours of the parathyroids, pancreas and pituitary. The MEN1 gene, which is located on chromosome 11q13 and encodes a 610 amino acid protein (menin), belongs to the class of tumour suppressors. To investigate the role of menin in tumour suppression, three different mouse models have been generated through targeted disruption of the Men1 gene. ...