Endocrine Abstracts

In recent years, there has been significant progress in defining the genetic aetiology of neonatal diabetes (NDM). It is likely that all cases result from single gene disorders since markers of autoimmunity associated with polygenic type 1 diabetes are rare in patients diagnosed before 6 months.Activating mutations in the KCNJ11 and ABCC8 genes encoding the Kir6.2 and SUR1 subunits of the β-cell ATP sensitive potassium (KATP...

The opposite phenotypes of diabetes and hyperinsulinism can be caused by different types of mutations within the same genes. For example, rare activating GCK gene mutations cause hyperinsulinism whereas the more common loss-of function mutations result in mild fasting hyperglycaemia in the heterozygous state or recessively inherited permanent neonatal diabetes.The knowledge that inactivating mutations in the KCNJ11 and ABCC8 genes en...

Hypophosphatemic rickets is a genetically heterogeneous disorder of defective renal phosphate transport and vitamin D metabolism with an X-linked dominant (XLHR), autosomal-dominant (ADHR) or autosomal-recessive (ARHR) pattern of inheritance. Germline mutations in the PHEX gene are associated with the X-linked form which affects both males and females. The autosomal dominant form is characterised by mutations in the FGF23 gene and the autosomal recessive form by ...

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by various combinations of tumours of the parathyroid, enteropancreatic and anterior pituitary glands. With the identification of the MEN1 gene, the genetic diagnosis of this condition is now possible. In this study, we have examined whether different clinical presentations of MEN1 are more likely to yield positive mutation result.Methods: We analysed t...

Diabetes arising in young adulthood has a wide differential diagnosis, including autoimmune and genetic causes as well as young onset type 2 diabetes (YT2D). Specific features may be associated with each of these groups, but they cannot be differentiated from YT2D by mode of presentation. Family history, clinical characteristics and laboratory investigations provide complementary strategies to help dissect different known aetiologies.We studied 268 UK Ca...

Introduction: Mutations in the RET gene cause multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma (FMTC). The identification of a germline RET mutation aids clinical management, enables the identification and predictive testing of at risk family members and provides reassurance for mutation-negative family members. In the research setting, mutations in exons 5, 8, 10, 11, 13–16 of the RET gene have been ...

Background: Multiple Endocrine Neoplasia (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pancreas and pituitary. Recent consensus guidelines have recommended screening of MEN1 gene mutations in patients who have at least two of the parathyroid hyperplasia, pancreatic endocrine tumour or pituitary adenoma, or are suspicious of having MEN1 (multiple parathyroid tumours before age 30, recurrent hyperparathyroidism, gastrinoma or multiple isl...

Introduction: X-linked hypo-phosphataemic rickets is characterized by hypophosphataemia, vitamin D deficiency, poor bone and dental mineralization. Mutations occur within the PHEX gene. Currently 329 mutations have been sequenced1. We report a novel PHEX mutation in a female with hypophosphataemic rickets.Case report: A 12-year-old girl presented with, genu varum, short stature and a previous dental abscess. Investigatons showed hypophosphatae...

Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disease. The clinical heterogeneity may range from mild subtle hypoglycaemia to severe life threatening hypoglycaemia. The commonest genetic cause of congenital hyperinsulinism are mutations in the genes ABCC8 and KCNJ11 encoding the two subunits (SUR1 and Kir6.2 respectively) of the pancreatic β-cell KATP channel. In the Ashkenazi Jewish population two founder mutation...

Background: Multiple endocrine neoplasia (MEN) type 2B is an autosomal dominant condition characterised by aggressive medullary C cell tumours, phaeochromocytoma and a discrete physical appearance. A specific point mutation in the RET proto-oncogene is present in 95% cases; prophylactic thyroidectomy is recommended in the mutation carriers. Occasionally cases present with the characteristic physical appearance of MEN2B but no identifiable germline mutation or endocrinop...