Endocrine Abstracts

Background: Diabetes mellitus (DM) is one of the commonest chronic disorders of children, and Type 1 DM is the most frequent form of diabetes in children. Rarely DM is associated with other systemic features. DM and sensorineural deafness (SD) are features of rare syndromes like Wolfram syndrome, Rogers syndrome and Mitochondrial DM. Wolfram syndrome (also known as DIDMOAD syndrome) is caused by los of function mutations in the WFS1 gene and the clinical features include diabetes Insipidus, DM, optic atrophy and SD. Rogers syndrome is caused by mutations in the SLC19A2 gene and is characterised by the occurrence of megaloblastic anaemia, DM, and SD. Mitochondrial DM is caused by mutations in MT-TL-1 and patients have DM with mitochondrial disease.

Patient/methods: We report three unrelated families (two consanguineous and one non consanguineous) with six affected children with DM and sensorineural hearing loss. These patients do not have any developmental or eye abnormalities; nor do they have any mental or neurological disorders, nor any learning disabilities. Genomic DNA was extracted and amplified using polymerase chain reaction and the exons and the exon–intron boundaries were sequenced for possible mutations in WFS1, SLC19A2, and MT-TL1.

Result: No mutations were identified in the coding regions of the genes WFS1, SLC19A2, MT-TL1 to explain the clinical phenotype of these patients. This suggests that there might be another unidentified genetic aetiology in these patients to account for the phenotype.

Conclusion: In the three families, mutations in the known genes (WFS1, SLC19A2, and MT-TL1) which cause DM syndromes associated with SD have been excluded. This suggests that these patients may have other novel genetic causes for DM and SD. Further work including homozygosity mapping and whole exome sequencing are in progress to find the genetic mechanism of DM and SD in these patients.