Kivonat:
BACKGROUND: This article presents a clinically characterization of the
mitochondrial DNA mutation (A3243G) associated with maternally inherited diabetes
and deafness (MIDD) syndrome in two families. METHODS: Six patients with MIDD and
one mutation-positive relative with normal glucose tolerance (NGT) were examined.
Fasting serum C-peptide was measured in all subjects and compared with controls
having NGT (n = 14). C-peptide response to an intravenous glucose tolerance test
(IVGTT) was investigated in the diabetic patients not treated with insulin (n =
3) and in the mutation-positive healthy individual and compared with the
controls. RESULTS: The A3243G heteroplasmy value varied between 5 and 30%. All
A3243G carriers had HLA-DR1-DQ5 haplotype, and either the -DQ5 or the -DQ6
allele. The fasting and the serum C-peptide levels at 120 min during the IVGTT
did not differ between the A3243G carriers and the controls. A missing first
phase and a decreased total C-peptide response was detected in the
mutation-positive diabetics compared with controls (p < 0.0001). The same
abnormality was found in the A3243G carrier with NGT. Circulating islet cell
antibody (ICA) was present in three patients with MIDD. Glutamic acid
decarboxylase (GAD), tyrosine phosphatase-like protein IA-2 (IA-2) and
mitochondrial antibodies were missing. The diagnosis of MIDD was delayed in each
case. CONCLUSIONS: A missing first phase and a decreased total C-peptide response
during an IVGTT was characteristic for the A3243G mutation. The fasting C-peptide
level of the carriers did not differ from the controls. Circulating ICA was
present in some patients, but GAD, IA-2 and mitochondrial antibodies were absent.
All subjects had HLA-DR1-DQ5 haplotype, and either -DQ5 or -DQ6 alleles.