Endocrine Abstracts

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: Children with hypoglycaemia due to Congenital Hyperinsulinism (CHI) usually present in the neonatal period but late presentations also occur. The phenotype of late-presenting CHI has not been well described.Aim and methods: We have reviewed the clinical course of children (n=22) presenting with CHI after 1 month of age in relation to mode of presentation, rapid KATP genetic mutation analysis, neurodevelopment, clinical progr...

Background: HADH encodes for the enzyme 3-hydroxyacyl-coenzyme A dehydrogenase (HADH) and catalyses the penultimate reaction in the beta-oxidation of fatty acids. Mutations in the HADH gene have recently been described to cause protein sensitive hyperinsulinaemic hypoglycaemia (HH). Protein sensitive HH (specifically leucine sensitivity), is also associated with the hyperinsulinism-hyperammonaemia syndrome (HI/HA syndrome) caused by activating mutations of GLUD1 ...

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...

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...

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...

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...

Background: The availability of genetic testing has major implications for family management in MEN syndromes. In order to offer systematic genetic and endocrine screening for type 1 and type 2 MEN we invited patients with possible MEN syndromes to a dedicated clinic.Outcomes: In the first year 16 subjects (from 12 families) were seen, with a total of 28 previous or current tumours (12 hyperparathyroidism, 10 pituitary and 6 foregut tumours). Eight subje...

Background and aims: Most children with permanent neonatal diabetes (PNDM) have heterozygous mutations in KCNJ11, ABCC8 or INS genes if they have unrelated parents. Although homozygous mutations in GCK and ABCC8 have been described in the offspring of consanguineous parents the genetic aetiology in most of these cases remains unknown. We hypothesised that homozygous mutations in the INS gene could cause PNDM in these patients.<p class="ab...