Maternally Inherited Diabetes Mellitus: the Role of Mitochondrial DNA Defects

A mitochondrial tRNALeu(UUR) mutation at nucleotide 3,243 is known to be found in most patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) and has also been identified in several families with maternally inherited diabetes mellitus and hearing loss. We report here audiologic features in patients with hearing loss associated with the mutation. Four patients without and five with MELAS were studied. Most of the patients had bilateral progressive sensorineural hearing loss. The most common shape of the audiogram was sloping, while cases in the advanced stages had flat audiograms. Speech discrimination scores were generally poor and did not parallel the degree of hearing loss. The present study suggests that the lesion for hearing loss could include both cochlear and retrocochlear involvement, but does not demonstrate a significant difference in the audiologic findings between patients with and without MELAS.

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Association of the T14709C mutation of mitochondrial DNA with maternally inherited diabetes mellitus and/or deafness in an Italian family

Diabetic Medicine ◽

10.1046/j.1464-5491.2001.00429-2.x ◽

2001 ◽

Vol 18 (4) ◽

pp. 334-336 ◽

Cited By ~ 15

Author(s):

L. Rigoli ◽

F. Prisco ◽

R. A. Caruso ◽

D. Iafusco ◽

G. Ursomanno ◽

...

Keyword(s):

Diabetes Mellitus ◽

Mitochondrial Dna ◽

Italian Family ◽

Inherited Diabetes

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Mitochondrial DNA mutation at np 3243 in a family with maternally inherited diabetes mellitus

Acta Diabetologica ◽

10.1007/s005920050161 ◽

1999 ◽

Vol 36 (3) ◽

pp. 163-167 ◽

Cited By ~ 5

Author(s):

L. Rigoli ◽

D.C. Salpietro ◽

R.A. Caruso ◽

A. Chiarenza ◽

I. Barberi

Keyword(s):

Diabetes Mellitus ◽

Mitochondrial Dna ◽

Mitochondrial Dna Mutation ◽

Dna Mutation ◽

Inherited Diabetes

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THE ROLE OF HETEROPLASMY IN THE DIAGNOSIS AND MANAGEMENT OF MATERNALLY INHERITED DIABETES AND DEAFNESS

Endocrine Practice ◽

10.4158/ep-2019-0270 ◽

2020 ◽

Vol 26 (2) ◽

pp. 241-246 ◽

Cited By ~ 1

Author(s):

Katie Nahay Robinson ◽

Sari Terrazas ◽

Samantha Giordano-Mooga ◽

Neena A. Xavier

Keyword(s):

Diabetes Mellitus ◽

Mitochondrial Dna ◽

Gastrointestinal Disease ◽

Clinical Manifestations ◽

Mitochondrial Diseases ◽

Signs And Symptoms ◽

Mtdna Sequence ◽

Scientific Papers ◽

Organ Specific ◽

Inherited Diabetes

Objective: Maternally inherited diabetes and deafness (MIDD) is a rare diabetic syndrome mainly caused by a point mutation in the mitochondrial DNA (mtDNA), mt3243 adenine to guanine (A>G). The objective of this paper is to review the genetic inheritance, clinical manifestations, and treatment of patients with MIDD. Methods: The current review used a literature search of scientific papers on this rare syndrome. Results: mtDNA is primarily inherited through the maternal oocyte; therefore, the genetic abnormalities in MIDD are associated with maternal inheritance. Mitochondria contain circular mtDNA, which codes for various mitochondrial genes. The mtDNA can be heteroplasmic, containing more than one type of mtDNA sequence; if one of the mtDNAs contains the mt3243 A>G mutation, a patient may develop MIDD. Patients can inherit different amounts of mutated mtDNA and normal mtDNA that affect the severity of the clinical manifestations of MIDD. The most common clinical manifestations include diabetes mellitus, deafness, ophthalmic disease, cardiac disease, renal disease, gastrointestinal disease, short stature, and myopathies. In order to effectively treat patients with MIDD, it is important to recognize the underlying pathophysiology of this specific form of diabetes and the pathophysiology associated with the organ-specific complications present in this disease. Conclusion: The heteroplasmic inheritance of mutated mtDNA plays an important role in the clinical manifestations of various mitochondrial diseases, specifically MIDD. This review will alert endocrinologists of the signs and symptoms of MIDD and important clinical considerations when managing this disease. Abbreviations: ATP = adenosine triphosphate; CoQ10 = coenzyme Q10; MELAS = mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke; MIDD = maternally inherited diabetes and deafness; mtDNA = mitochondrial DNA; tRNA = transfer ribonucleic acid; ROS = reactive oxygen species; T2DM = type 2 diabetes mellitus

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Family Phenotypic Heterogeneity Caused by Mitochondrial DNA Mutation A3243G

Acta Médica Portuguesa ◽

10.20344/amp.8638 ◽

2017 ◽

Vol 30 (7-8) ◽

pp. 581 ◽

Cited By ~ 3

Author(s):

Daniela Alves ◽

Maria Eufémia Calmeiro ◽

Carmo Macário ◽

Rosa Silva

Keyword(s):

Diabetes Mellitus ◽

Hearing Loss ◽

Mitochondrial Dna ◽

Diagnostic Challenge ◽

Mitochondrial Dna Mutation ◽

Dna Mutation ◽

History Of ◽

Monogenic Forms Of Diabetes ◽

Inherited Diabetes ◽

Relevant Family History

Maternally inherited diabetes and deafness is a rare form of diabetes caused by a mitochondrial DNA mutation. The index case is a 55-year-old woman who was admitted with hypertrophic cardiomyopathy. She had a history of diabetes mellitus and hearing loss. The patient’s mother, two brothers and two sisters also had a history of diabetes and hearing loss. This pattern suggests a maternally inherited disorder. All siblings carried the A3243G mitochondrial DNA mutation. The identification of people with monogenic forms of diabetes mellitus is a diagnostic challenge. This condition should be considered whenever there is a history of diabetes associated with hearing loss and a relevant family history. Cardiopathy is also known to be an important feature of mitochondrial disease. In order to identify this aetiology, family screening, genetic counselling and screening of associated comorbidities are encouraged.

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