Mitochondrial diabetes in children: seek and you will find it.
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 2...
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2012
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oai:doaj.org-article:02e25c3275a64f338bc73c38a97977aa2021-11-18T07:21:38ZMitochondrial diabetes in children: seek and you will find it.1932-620310.1371/journal.pone.0034956https://doaj.org/article/02e25c3275a64f338bc73c38a97977aa2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22536343/?tool=EBIhttps://doaj.org/toc/1932-6203Maternally 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.Cristina MazzaccaraDario IafuscoRosario LiguoriMaddalena FerrignoAlfonso GalderisiDomenico VitaleFrancesca SimonelliPaolo LandolfoFrancesco PriscoMariorosario MasulloLucia SacchettiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34956 (2012) |
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Medicine R Science Q |
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Medicine R Science Q Cristina Mazzaccara Dario Iafusco Rosario Liguori Maddalena Ferrigno Alfonso Galderisi Domenico Vitale Francesca Simonelli Paolo Landolfo Francesco Prisco Mariorosario Masullo Lucia Sacchetti Mitochondrial diabetes in children: seek and you will find it. |
| description |
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. |
| format |
article |
| author |
Cristina Mazzaccara Dario Iafusco Rosario Liguori Maddalena Ferrigno Alfonso Galderisi Domenico Vitale Francesca Simonelli Paolo Landolfo Francesco Prisco Mariorosario Masullo Lucia Sacchetti |
| author_facet |
Cristina Mazzaccara Dario Iafusco Rosario Liguori Maddalena Ferrigno Alfonso Galderisi Domenico Vitale Francesca Simonelli Paolo Landolfo Francesco Prisco Mariorosario Masullo Lucia Sacchetti |
| author_sort |
Cristina Mazzaccara |
| title |
Mitochondrial diabetes in children: seek and you will find it. |
| title_short |
Mitochondrial diabetes in children: seek and you will find it. |
| title_full |
Mitochondrial diabetes in children: seek and you will find it. |
| title_fullStr |
Mitochondrial diabetes in children: seek and you will find it. |
| title_full_unstemmed |
Mitochondrial diabetes in children: seek and you will find it. |
| title_sort |
mitochondrial diabetes in children: seek and you will find it. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/02e25c3275a64f338bc73c38a97977aa |
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