A detailed investigation of maternally inherited diabetes and deafness (MIDD) including clinical characteristics, C‐peptide secretion, HLA‐DR and ‐DQ status and autoantibody pattern

Hosszúfalusi, Nóra; Karcagi, Veronika; Horváth, Rita; Palik, Éva; Várkonyi, Judit; Rajczy, Katalin; Prohászka, Zoltán; Szentirmai, Csaba; Karádi, István; Romics, L; Pánczél, Pál

doi:10.1002/dmrr.841

Cited by 10 publications

(2 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In studies conducted in adults, young adults, in family case reports and in the MIDD 1 form, diabetes was usually diagnosed in patients aged between 16 and 43 years [1], [6], [24], [25]. The age at MIDD onset is also related to the heteroplasmy level of the mutations.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Diabetes in Children: Seek and You Will Find It

et al. 2012

View full text Add to dashboard Cite

Maternally Inherited Diabetes and Deafness (MIDD) is a rare form of diabetes due to defects in mitochondrial DNA (mtDNA). 3243 A>G is the mutation most frequently associated with this condition, but other mtDNA variants have been linked with a diabetic phenotype suggestive of MIDD. From 1989 to 2009, we clinically diagnosed mitochondrial diabetes in 11 diabetic children. Diagnosis was based on the presence of one or more of the following criteria: 1) maculopathy; 2) hearing impairment; 3) maternal heritability of diabetes/impaired fasting glucose and/or hearing impairment and/or maculopathy in three consecutive generations (or in two generations if 2 or 3 members of a family were affected). We sequenced the mtDNA in the 11 probands, in their mothers and in 80 controls. We identified 33 diabetes-suspected mutations, 1/33 was 3243A>G. Most patients (91%) and their mothers had mutations in complex I and/or IV of the respiratory chain. We measured the activity of these two enzymes and found that they were less active in mutated patients and their mothers than in the healthy control pool. The prevalence of hearing loss (36% vs 75–98%) and macular dystrophy (54% vs 86%) was lower in our mitochondrial diabetic adolescents than reported in adults. Moreover, we found a hitherto unknown association between mitochondrial diabetes and celiac disease. In conclusion, mitochondrial diabetes should be considered a complex syndrome with several phenotypic variants. Moreover, deafness is not an essential component of the disease in children. The whole mtDNA should be screened because the 3243A>G variant is not as frequent in children as in adults. In fact, 91% of our patients were mutated in the complex I and/or IV genes. The enzymatic assay may be a useful tool with which to confirm the pathogenic significance of detected variants.

show abstract

Section: Discussionmentioning

confidence: 99%

Mitochondrial Diabetes in Children: Seek and You Will Find It

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Although, in general, patients with MIDD show lower insulin secretory capacity and need insulin therapy to manage hyperglycemia, usually they retain some residual CPR level [1]. Hosszufalusi et al reported that there is a loss of first phase and total CPR response but measurable fasting CPR (0.79-6.57 ng/ml) during an intravenous glucose tolerance test (IVGTT) in patients with MIDD compared with nondiabetic controls [6]. Guillausseau et al reported that 17% of patients with MIDD were insulin-dependent from the onset, with ketoacidosis in 8% of patients, while in the others (83%) diabetes resembled type 2 diabetes [7], suggesting that there is heterogeneity of the diabetic phenotype in patients with MIDD, although the CPR levels of the patients were not reported.…”

Section: Case Reportmentioning

confidence: 99%

Maternally Inherited Diabetes and Deafness (MIDD) with Undetectable CPeptide Level and Cerebellar Atrophy

Saisho

Inaishi²

2014

J Clin Case Rep

View full text Add to dashboard Cite

Maternally inherited diabetes and deafness (MIDD), also called mitochondrial diabetes mellitus, is a rare form of diabetes that comprises 0.5-2.8% of the diabetic population. Most cases of MIDD are associated with a point mutation in the mitochondrial DNA (mtDNA) at position 3243 of the leucine tRNA gene (A3243G) . Patients with MIDD are characterized by 1) young onset of diabetes, 2) absence of obesity, 3) neurosensory hearing loss, 4) maternal family history of diabetes and 5) progressive insulin secretory defect. In most cases of MIDD, diabetes is non-insulin dependent at onset, but progresses to require insulin therapy thereafter. However, to our knowledge, few cases with MIDD show complete loss of C-peptide level during the course of the disease. Case ReportMaternally Inherited Diabetes and Deafness (MIDD), also called mitochondrial diabetes mellitus, is a rare form of diabetes that comprises 0.5-2.8% of the diabetic population [1][2][3][4]. Most cases of MIDD are associated with a point mutation in the mitochondrial DNA (mtDNA) at position 3243 of the leucine tRNA gene (A3243G) [2][3][4]. Patients with MIDD are characterized by 1) young onset of diabetes, 2) absence of obesity, 3) neurosensory hearing loss, 4) maternal family history of diabetes and 5) progressive insulin secretory defect [1][2][3]5]. In most cases of MIDD, diabetes is non-insulin-dependent at onset, but progresses to require insulin therapy thereafter. However, to our knowledge, few cases of MIDD show complete loss of C-peptide during the course of the disease.The case was a 42-year-old Japanese man. At the age of 34, he attended our clinic because of thirst, polydipsia and weight loss (5 kg in 6 months), and was diagnosed with diabetes (plasma glucose 436 mg/dl, HbA1c 18.2%). He showed a short, lean stature (1.54 m, 41 kg, BMI 17.3) and had had neurosensory hearing loss since childhood treated with a hearing aid. His mother also had diabetes and hearing loss, and he showed mtDNA A3243G mutation. Islet-related autoantibodies (glutamic acid decarboxylase (GAD) and insulinomaassociated protein-2 (IA-2) antibodies) were negative. He was diagnosed with MIDD and insulin therapy was started. Under basalbolus insulin therapy, his HbA1c level decreased to ~7%. He also had an older sister with hearing loss but not diabetes, although it was not possible to perform genetic testing in his family members.At the time of diagnosis, serum C-peptide immnoreactivity (CPR) level was 1.1-5.3 ng/ml. However, CPR level gradually declined and became undetectable (<0.05 ng/ml) from the age of 38. Although HbA1c level remained at 7-8%, he was admitted to our hospital at the age of 42 because of repeated episodes of hypoglycemia. At this time, he was treated with insulin lispro 5 U before each meal and insulin glargine 7 U at bedtime. He had neither diabetic retinopathy nor macular pattern dystrophy, but had microalbuminuria (32.7 mg/g creatinine) and diabetic neuropathy. Serum CPR and 24 h urinary CPR were both undetectable (<0.05 ng/ml and <2 μg/day, re...

show abstract

Current literature in diabetes

2009

Diabetes Metabolism Res

View full text Add to dashboard Cite

In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author

show abstract

A detailed investigation of maternally inherited diabetes and deafness (MIDD) including clinical characteristics, C‐peptide secretion, HLA‐DR and ‐DQ status and autoantibody pattern

Cited by 10 publications

References 29 publications

Mitochondrial Diabetes in Children: Seek and You Will Find It

Mitochondrial Diabetes in Children: Seek and You Will Find It

Maternally Inherited Diabetes and Deafness (MIDD) with Undetectable CPeptide Level and Cerebellar Atrophy

Current literature in diabetes

Contact Info

Product

Resources

About