Wolfram or DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and 
Deafness) syndrome, which has long been known as an autosomal-recessive 
disorder, has recently been proposed to be a mitochondrial-mediated disease with 
either a nuclear or a mitochondrial genetic background. The phenotypic 
characteristics of the syndrome resemble those found in other mitochondrial 
(mt)DNA mediated disorders such as Leber's hereditary optic neuropathy (LHON) or 
maternally inherited diabetes and deafness (MIDD). Therefore, we looked for 
respective mtDNA alterations in blood samples from 7 patients with DIDMOAD 
syndrome using SSCP-analysis of PCR-amplified fragments, encompassing all 
mitochondrial ND and tRNA genes, followed by direct sequencing. Subsequently, we 
compared mtDNA variants identified in this disease group with those detected in 
a group of LHON patients (n = 17) and in a group of 69 healthy controls. We 
found that 4/7 (57%) DIDMOAD patients harbored a specific set of point mutations 
in tRNA and ND genes including the so-called class II or secondary LHON 
mutations at nucleotide positions (nps) 4216 and 4917 (haplogroup B). In 
contrast, LHON-patients were frequently (10/17, 59%) found in association with 
another cluster of mtDNA variants including the secondary LHON mutations at nps 
4216 and 13708 and further mtDNA polymorphisms in ND genes (haplogroup A), 
overlapping with haplogroup B only by variants at nps 4216 and 11251. The 
frequencies of both haplogroups were significantly lower in the control group 
versus the respective disease groups. We propose that haplogroup B represents a 
susceptibility factor for DIDMOAD which, by interaction with further exogeneous 
or genetic factors, might increase the risk for disease.