Contrasting features of insulin dependent diabetes mellitus associated with neuroectodermal defects and classical insulin dependent diabetes mellitus.

The Wolfram, or DIDMOAD, syndrome is a rare congenital disease that is associated with diabetes insipidus, insulin dependent diabetes mellitus of an early onset, bilateral optic atrophy and deafness. Urological disorders are usually present as well. We have studied nine patients belonging to five different families. All of the family members were HLA typed (including DR), and islet cell as well as antinuclear antibody determinations were carried out. Although individuals with insulin dependent diabetes mellitus are very prone to have either HLA-DR3 or -DR4 antigens, none of our patients had DR3 antigens and only one was DR4 positive. On the other hand, three of our patients were typed as HLA-DR2 positive. This antigen is uncommon in classical insulin dependent diabetes. In one of the families, the affected siblings did not share the same HLA haplotype. Islet cell and antinuclear antibodies were not found in any of the cases and six of the patients had a small, but significant, insulin secretory reserve. On the basis of some of the clinical features it was also possible to further distinguish between the DIDMOAD syndrome and the classical insulin dependent diabetes mellitus. The differences encountered between classical and DIDMOAD insulin dependent diabetes mellitus--the presence/absence of HLA linkage, HLA-DR2, -DR3 and -DR4 associations, islet cell or antinuclear antibodies, the tendency to ketosis and diabetic retinopathy--indicate that their etiopathogenies are triggered by distinct mechanisms.