title: A detailed investigation of maternally inherited diabetes and deafness (MIDD) including clinical characteristics, C-peptide secretion, HLA-DR and -DQ status and autoantibody pattern.
abstract: 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.
authors.affiliation: Semmelweis University, Budapest, 3rd Department of Internal Medicine, Budapest, Hungary. hono@kut.sote.hu
authors.forename: Nóra
authors.initials: N
authors.lastname: Hosszúfalusi
authors.forename: Veronika
authors.initials: V
authors.lastname: Karcagi
authors.forename: Rita
authors.initials: R
authors.lastname: Horváth
authors.forename: Eva
authors.initials: E
authors.lastname: Palik
authors.forename: Judit
authors.initials: J
authors.lastname: Várkonyi
authors.forename: Katalin
authors.initials: K
authors.lastname: Rajczy
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Prohászka
authors.forename: Csaba
authors.initials: C
authors.lastname: Szentirmai
authors.forename: István
authors.initials: I
authors.lastname: Karádi
authors.forename: László
authors.initials: L
authors.lastname: Romics
authors.forename: Pál
authors.initials: P
authors.lastname: Pánczél
mesh_terms: D000328:Adult; D002096:C-Peptide / Q000097:blood*; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics*; D003638:Deafness / Q000150:complications / Q000235:genetics* / Q000276:immunology; D048909:Diabetes Complications / Q000235:genetics / Q000276:immunology; D003920:Diabetes Mellitus / Q000235:genetics* / Q000382:microbiology; D005190:Family; D005260:Female; D005951:Glucose Tolerance Test; D006683:HLA-DQ Antigens / Q000032:analysis*; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009035:Mothers; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D002096:C-Peptide; D017931:DNA Primers; D004272:DNA, Mitochondrial; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens