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Mitochondrial Diabetes Diagnosis

Pyruvate Improved Insulin Secretion Status In A Mitochondrial Diabetes Mellitus Patient

Pyruvate Improved Insulin Secretion Status In A Mitochondrial Diabetes Mellitus Patient

Mitochondrial diabetes is a rare form of diabetes mellitus accounting for up to 1% of all diabetes. Pyruvate therapy has been reported to be a potential therapeutic choice for patients with mitochondrial diseases. Water-based sodium pyruvate solutions (0.5 g/kg, thrice daily) were administrated orally to a 32-year-old Japanese male with mitochondrial diabetes and myopathy caused by m.14709T>C mutation. At the age of 20 years, he was diagnosed with diabetes mellitus and started insulin therapy. He tested negative for islet cell and glutamic decarboxylase antibodies. To evaluate favorable therapeutic improvements, we measured the lactate and pyruvate levels in plasma and cerebrospinal fluid; urinary C-peptide, glycated hemoglobin, and glycoalbumin levels; and total daily insulin dose (TDD). The patient experienced no side effects such as diarrhea because of pyruvate therapy. His urinary C-peptide level improved from 4.3 to 17.2 g/d after 1 day and to 30.2 g/d after 6 months of pyruvate therapy. TDD decreased from 33 to 20 U/d after 6 months of pyruvate therapy, but the lactate levels of plasma and cerebrospinal fluid and the lactate/pyruvate ratio did not change. Sodium pyruvate improved insulin secretion and resulted in decreased TDD in a patient with mitochondrial diabetes. Pyruvate therapy may be a potential therapeutic choice for patients with mitochondrial diabetes. Clinical trials involving a larger number of patients and long-term evaluation of the therapy are necessary to clarify the efficacy of pyruvate therapy. In a mitochondrial disorder, there is a metabolic block in oxidative phosphorylation; this disorder shows a large spectrum of symptoms, such as muscle weakness, encephalopathy, impaired hearing, and diabetes mellitus (DM). Dysfunctional mitochondria in t Continue reading >>

Payperview: Diabetes Mellitus In Mitochondrial Disease - Karger Publishers

Payperview: Diabetes Mellitus In Mitochondrial Disease - Karger Publishers

Diabetes Mellitus in Mitochondrial Disease Prof. Robert W. Taylor or Dr. Andrew M. Schaefer Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience The Medical School, Newcastle University, Framlington Place E-Mail [email protected], [email protected] I have read the Karger Terms and Conditions and agree. Mitochondrial diseases arise as a consequence of respiratory chain dysfunction caused by mutations in the mitochondrial genome (mtDNA) or nuclear-encoded mitochondrial genes. Multisystem involvement is a hallmark of many subtypes of mitochondrial disease in which energy-dependent organs including the brain, skeletal muscles, and heart are commonly affected. The most common mitochondrial genotype that causes diabetes mellitus is a single nucleotide substitution (m.3243A>G) in the mitochondrial tRNALeu(UUR) gene which is linked to a distinctive clinical phenotype - maternally inherited diabetes and deafness. Diabetes mellitus often arises insidiously as part of the clinical presentation associated with mitochondrial disease; however, there are unique clinical features and associated complications compared to other diabetes subtypes. Overall, the treatment of patients with mitochondrial diabetes is similar to those with other causes of diabetes but with additional emphasis on the screening and subsequent management of additional multiorgan involvement. Ballinger SW, Shoffner JM, Hedaya EV, Trounce I, Polak MA, Koontz DA, et al: Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion. Nat Genet 1992;1:11-15. van den Ouweland JM, Lemkes HH, Ruitenbeek W, Sandkuijl LA, de Vijlder MF, Struyvenberg PA, et al: Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally tra Continue reading >>

Mitochondrial Diseases

Mitochondrial Diseases

Overview Diagnosis and Tests Management and Treatment Outlook / Prognosis Mitochondria are the energy factory of our body. Several thousand mitochondria are in nearly every cell in the body. Their job is to process oxygen and convert substances from the foods we eat into energy. Mitochondria produce 90 percent of the energy our body needs to function. Mitochondrial diseases are chronic, genetic, often inherited disorders that occur when mitochondria fail to produce enough energy for the body to function properly. (Inherited means the disorder was passed on from parents to children.) Mitochondrial diseases can be present at birth, but can also occur at any age. Mitochondrial diseases can affect almost any part of the body including the cells of the brain, nerves, muscles, kidneys, heart, liver, eyes, ears or pancreas. Mitochondrial dysfunction occurs when the mitochondria do not work as well as they should due to another disease or condition. Many conditions can lead to secondary mitochondrial dysfunction including autism , Parkinsons disease , Alzheimers disease , muscular dystrophy , Lou Gehrigs disease , diabetes , and cancer. Individuals with secondary mitochondrial dysfunction do not have primary genetic mitochondrial disease and do not need to be concerned about the ongoing development or worsening of symptoms. One in 5,000 individuals has a mitochondrial disease. Each year, about 1,000 to 4,000 children in the United States are born with a mitochondrial disease. With the number and type of symptoms and organ systems involved, mitochondrial diseases are often mistaken for other, more common, diseases. In most people, primary mitochondrial disease is a genetic condition that can be inherited (passed from parents to their children). Mitochondrial diseases can be inh Continue reading >>

Maternally-inherited Diabetes With Deafness (midd) And Hyporeninemic Hypoaldosteronism

Maternally-inherited Diabetes With Deafness (midd) And Hyporeninemic Hypoaldosteronism

CASE REPORT Diabetes mitocondrial (MIDD) e hipoaldosteronismo hiporreninêmico Patricia B. Mory; Marcia C. dos Santos; Claudio E. Kater; Regina S. Moisés Disciplina de Endocrinologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp-EPM), São Paulo, SP, Brazil SUMMARY Maternally-inherited diabetes with deafness (MIDD) is a rare form of monogenic diabetes that results, in most cases, from an A-to-G transition at position 3243 of mitochondrial DNA (m.3243A>G) in the mitochondrial-encoded tRNA leucine (UUA/G) gene. As the name suggests, this condition is characterized by maternally-inherited diabetes and bilateral neurosensory hearing impairment. A characteristic of mitochondrial cytopathies is the progressive multisystemic involvement with the development of more symptoms during the course of the disease. We report here the case of a patient with MIDD who developed hyporeninemic hypoaldosteronism. Arq Bras Endocrinol Metab. 2012;56(8):574-7 SUMÁRIO O diabetes mitocondrial (MIDD) é uma forma rara de diabetes monogênico resultante, na maioria dos casos, da mutação mitocondrial A3243G. Essa condição é caracterizada por diabetes de transmissão materna e disacusia neurossensorial. Uma característica das mitocondriopatias é o envolvimento progressivo de outros órgãos ou sistemas, levando ao aparecimento de diversos sintomas durante o curso da doença. Este relato descreve o caso de um paciente com MIDD que, durante o período de acompanhamento, apresentou hipoaldosteronismo hiporreninêmico. Arq Bras Endocrinol Metab. 2012;56(8):574-7 INTRODUCTION Maternally inherited diabetes and deafness (MIDD) (OMIM # 520000) is a rare form of diabetes that results, in most cases, from an A-to-G transition at position 3243 of mitochondrial DNA (m.3243A> Continue reading >>

Mitochondrial Diabetes: Clinical Specificity And Diagnosis

Mitochondrial Diabetes: Clinical Specificity And Diagnosis

Mitochondrial Diabetes: Clinical Specificity and Diagnosis Diabetes cannot be considered any more as an unique disease. Even in so called type 2 diabetes (non insulin-dependent diabetes) multiple etiologies can concur to this common clinical expression. During the last decade, progress in molecular biology have allowed the identification of monogenic forms of diabetes. Mitochondrial diabetes, as the MODY type diabetes (maturity onset diabetes in the young), belongs to this family of diabetes caused by one abnormal gene. Beta CellDiabetic RetinopathyBuccal MucosaA3243G MutationMitochondrial Disorder These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves. This is a preview of subscription content, log in to check access. Unable to display preview. Download preview PDF. Van den Ouweland JMW, Lemkes HHPJ, Ruittenbeck W, Sandkkuijl LA, de Wijlder M, Struyvenberg PA et al. (1992); Mutation in mitochondrial tRNA Leu(UUR) gene in a large pedigree with maternally transmitted type 2 diabetes mellitus and deafness. Nat Genet, 1: 36871. PubMed CrossRef Google Scholar Reardon W, Ross RJM, Sweeney MG, Luxon L, Pembrey ME, Harding AE et al. (1992). Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA. Lancet, 340: 13769. PubMed CrossRef Google Scholar Maassen JA, van den Ouweland JM, t'Hart LM, Lemkes HH (1997). Maternally inherited diabetes and deafness: a diabetic subtype associated with a mutation in mitochondrial DNA. Horm Metab Res, 29: 505. PubMed CrossRef Google Scholar Kadowaki T, Kadowaki H, Mori Y, Tobe K, Sakuta R, Suzuki Y et al. (1994). A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA. New Engl J Med\ 330: 9628. Continue reading >>

Type 1 Diabetic With Mitochondrial Disease

Type 1 Diabetic With Mitochondrial Disease

Diabetes Forum The Global Diabetes Community This site uses cookies. By continuing to use this site, you are agreeing to our use of cookies. Learn More. Get the Diabetes Forum App for your phone - available on iOS and Android . Find support, ask questions and share your experiences. Join the community Type 1 diabetic with mitochondrial disease Hey guys! So I have been diabetic now for nearly three years. Since being diagnosed they have discovered that I actually suffer from a condition called MIDD (maternally inherited diabetes and deafness) this form of diabetes is a mitochondrial form meaning that I will eventually loose some of my hearing. As well as the diabetes side of it I also suffer from muscle pains and I awaiting a muscle biopsy. I was hoping I could find people my age and possibly who might live in the newcastle area to chat with or just people in general who suffer similarly I don't have MIDD, but understand that there is a Professor in Newcastle who is an expert on this condition, you may have already been referred to him ? It's quite rare ! But a warm welcome to the forum, I know that you will find a huge amount of info here on the diabetes side alone that you will find of interest, also a great deal of support Welcome. I hope you get all the answers and support you need. ( Because I'm pretty sure someone posted about this recently , I just can't remember who and where There is another forum member who posted about this condition, @kesun , but it was a few months back. Her post is here, Thank you Catherine, I knew that I had read it somewhere ! However, " recent" could be anytime in the last decade for me Hey guys! So I have been diabetic now for nearly three years. Since being diagnosed they have discovered that I actually suffer from a condition called Continue reading >>

Omim Entry - # 520000 - Diabetes And Deafness, Maternally Inherited; Midd

Omim Entry - # 520000 - Diabetes And Deafness, Maternally Inherited; Midd

A number sign (#) is used with this entry because of evidence that the disorder can be caused by mutation in several mitochondrial genes, including MTTL1 ( 590050 ), MTTE ( 590025 ), and MTTK ( 590060 ). The most common mutation is a 3243A-G transition in the MTTL1 gene ( 590050.0001 ). Maternally inherited diabetes-deafness syndrome (MIDD) is a mitochondrial disorder characterized by onset of sensorineural hearing loss and diabetes in adulthood. Some patients may have additional features observed in mitochondrial disorders, including pigmentary retinopathy, ptosis, cardiomyopathy, myopathy, renal problems, and neuropsychiatric symptoms ( Ballinger et al., 1992 ; Reardon et al., 1992 ; Guillausseau et al., 2001 ). The association of diabetes and deafness is observed with Wolfram syndrome (see 222300 ), Rogers syndrome ( 249270 ), and Herrmann syndrome ( 172500 ), but all 3 of these disorders have other clinical manifestations. Kressmann (1976) reported a large family in which diabetes and deafness were transmitted over 4 generations, with a total of 13 affected individuals. The clinical history was the same for all affected patients: the first manifestation was deafness, beginning at 20 to 30 years of age, with a rapid and severe increase in bilateral sensory hearing loss. Diabetes mellitus developed later in the third decade, and insulin was required either immediately or at a later date. At that time, persons from the fourth generation who were less than 20 years of age presented no deafness or diabetes. No pedigree member had ptosis, ophthalmoplegia, or muscle weakness. Reexamination of members of the family by Negrier et al. (1998) demonstrated no ragged-red fibers on skeletal muscle biopsy specimens and very limited lipid storage on electron microscopy. Ballinger Continue reading >>

Diagnosis Of Maternally Inherited Diabetes And Deafness (mitochondrial A3243g Mutation) Based On Funduscopic Appearance In An Asymptomatic Patient

Diagnosis Of Maternally Inherited Diabetes And Deafness (mitochondrial A3243g Mutation) Based On Funduscopic Appearance In An Asymptomatic Patient

Case description A 68-year-old man presented to our service for routine retinal evaluation. His medical history included asthma and hypothyroidism, which were well controlled with medication. His ocular history included mild cataracts, floaters and non-neovascular age-related macular degeneration that was diagnosed by a comprehensive ophthalmologist several years earlier. The patient expressed no systemic complaints. The patient stated that his family members were all in good health. On examination, his best-corrected visual acuity was 20/25 bilaterally. Amsler grid testing revealed central metamorphopsia in the right eye. Anterior segment examination showed early lens opacities in both eyes. Funduscopic examination revealed bilateral areas of geographic retinal pigment epithelium loss within the macula. Small subretinal vitelliform lesions were present along the superotemporal arcades (figure 1). There were no peripheral retinal abnormalities detected in either eye. Fundus autofluorescence (FAF) imaging showed geographic areas of macular and peripapillary hypo-autofluorescence with speckled areas of hyper-autofluorescence corresponding to the subretinal vitelliform … Continue reading >>

Mitochondrial Diabetes

Mitochondrial Diabetes

GENE DIAGNOSTICS University of Eastern FinlandJoensuu | Kuopio | Savonlinna Diabetes is a common manifestation in mitochondrial diseases caused by mutations in mtDNA. The most important mutation is the m.3243A>G substitution in the MTTL1 gene, which leads to hearing loss and diabetes at a young age. Diabetes resembles type 2 diabetes. Impaired insulin secretion is a typical finding. Typically, mitochondrial diabetes is associated with normal weight and the disease is diagnosed between 20 and 45 years of age. In an unselected sample, the prevalence of mitochondrial diabetes is less than 1%, but around 2 to 2.5% if diabetes is inherited from the maternal side. Mitochondrial diabetes should be particularly suspected in adults having both diabetes and hearing impairment. The prevalence of the mutation m.3243A>G can be up to 60% in these subjects. The level of heteroplasmy of the mutation in the blood sample is often low, and the mutation cannot always be demonstrated in the DNA. In these cases the mutation is found in other tissues, e.g. skeletal muscle. The analysis is performed from a whole blood sample (EDTA). Instructions for storage and sending the sample as well as prices for DNA screening are given in the request form. The report and interpretation of the results are mailed to the address given in the order 6-8 weeks after the arrival of the blood sample. Continue reading >>

Orphanet: Mitochondrial Diabetes

Orphanet: Mitochondrial Diabetes

The prevalence is unknown, but MIDD accounts for 0.2-3% of all cases of diabetes. The first manifestations may occur at any age, but the disease is usually diagnosed in early adulthood. In most cases, the onset of deafness precedes that of diabetes. The severity of the hearing loss is variable but it is sensorineural, bilateral and progressive, and is more profound at higher frequencies. In most cases, patients present pseudo-type 2 diabetes, with a normal or low body mass index. Pseudo-type 1 diabetes, sometimes with ketoacidosis, is observed in 20% of cases. Diabetic retinopathy is less common in MIDD patients than in those with classic forms of diabetes. In more than 80% of cases, patients develop specific macular pattern dystrophy lesions that are only seen in MIDD patients and are asymptomatic in most cases. Organs with high metabolic activity (muscles, myocardium, kidney, and brain) are frequently affected potentially leading to muscle pain, gastrointestinal tract symptoms, nephropathy, cardiomyopathy, and neuropsychiatric symptoms. In most cases, MIDD is caused by a point mutation in the mitochondrial gene MT-TL1, encoding the mitochondrial tRNA for leucine, and in rare cases in MT-TE and MT-TK genes, encoding the mitochondrial tRNAs for glutamic acid, and lysine, respectively. Diagnosis is based on the clinical picture and patient history. Measurements of fasting plasma glucose levels allow diagnosis of the diabetes. Ophthalmologic examination reveals the disease-specific macular pattern dystrophy. The diagnoses of standard type 2 and type 1 diabetes are excluded by the presence of the deafness, low body weight and the specific macular pattern dystrophy, and by evidence of maternal transmission. Management is symptomatic. Oral antidiabetic agentsand/or insulin Continue reading >>

Mitochondrial Disorder Medical Information

Mitochondrial Disorder Medical Information

Mitochondrial Disorder Medical Information Visit the BCMJ May 2011 issue here to read a compilation of medical articles about mitochondrial disease. A mitochondrion (singular of mitochondria) is part of every cell in the body that contains genetic material. Mitochondria are responsible for processing oxygen and converting substances from the foods we eat into energy for essential cell functions. Mitochondria produce energy in the form of adenosine triphosphate (ATP), which is then transported to the cytoplasm of a cell for use in numerous cell functions. What are mitochondrial and metabolic diseases? Mitochondrial medicine is a new and rapidly developing medical subspecialty. Many specialists are involved in researching mitochondrial diseases, including doctors specializing in metabolic diseases, cell biologists, molecular geneticists, neurologists, biochemists, pathologists, immunologists, and embryologists. Much of what we know about these diseases has been discovered since 1940. In 1962, the first patient was diagnosed with a mitochondrial disorder. In 1963, researchers discovered that mitochondria have their own DNA or "blueprint" (mtDNA), which is different than the nuclear DNA (nDNA) found in the cells' nucleus. Mitochondrial and metabolic medical conditions are now referred to as mitochondrial cytopathies. Mitochondrial cytopathies actually include more than 40 different identified diseases that have different genetic features. The common factor among these diseases is that the mitochondria are unable to completely burn food and oxygen in order to generate energy. The process of converting food and oxygen (fuel) into energy requires hundreds of chemical reactions, and each chemical reaction must run almost perfectly in order to have a continuous supply of energy Continue reading >>

Unexplained Gastrointestinal Symptoms: Think Mitochondrial Disease - Sciencedirect

Unexplained Gastrointestinal Symptoms: Think Mitochondrial Disease - Sciencedirect

Volume 46, Issue 1 , January 2014, Pages 1-8 Unexplained gastrointestinal symptoms: Think mitochondrial disease Defects in mitochondrial function are increasingly recognised as central to the pathogenesis of many diseases, both inherited and acquired. Many of these mitochondrial defects arise from abnormalities in mitochondrial DNA and can result in multisystem disease, with gastrointestinal involvement common. Moreover, mitochondrial disease may present with a range of non-specific symptoms, and thus can be easily misdiagnosed, or even considered to be non-organic. We describe the clinical, histopathological and genetic findings of six patients from three families with gastrointestinal manifestations of mitochondrial disease. In two of the patients, anorexia nervosa was considered as an initial diagnosis. These cases illustrate the challenges of both diagnosing and managing mitochondrial disease and highlight two important but poorly understood aspects, the clinical and the genetic. The pathophysiology of gastrointestinal involvement in mitochondrial disease is discussed and emerging treatments are described. Finally, we provide a checklist of investigations for the gastroenterologist when mitochondrial disease is suspected. Continue reading >>

Mitochondrial Myopathies (mm)

Mitochondrial Myopathies (mm)

None of the hallmark symptoms of mitochondrial disease muscle weakness, exercise intolerance, hearing impairment, ataxia, seizures, learning disabilities, cataracts, heart defects, diabetes and stunted growth are unique to mitochondrial disease. However, a combination of three or more of these symptoms in one person strongly points to mitochondrial disease, especially when the symptoms involve more than one organ system. To evaluate the extent of these symptoms, a physician usually begins by taking the patients personal medical history, and then proceeds with physical and neurological exams. At the bottom of this page is a chart that explains in detail these tests and what they are expected to show. Diagnostic tests in mitochondrial diseases The physical exam typically includes tests of strength and endurance, such as an exercise test, which can involve activities like repeatedly making a fist, or climbing up and down a small flight of stairs. The neurological exam can include tests of reflexes, vision, speech and basic cognitive (thinking) skills. Depending on information found during the medical history and exams, the physician might proceed with more specialized tests that can detect abnormalities in muscles, brain and other organs. The most important of these tests is the muscle biopsy , which involves removing a small sample of muscle tissue to examine. When treated with a dye that stains mitochondria red, muscles affected by mitochondrial disease often show ragged red fibers muscle cells (fibers) that have excessive mitochondria. Other stains can detect the absence of essential mitochondrial enzymes in the muscle. Its also possible to extract mitochondrial proteins from the muscle and measure their activity. In addition to the muscle biopsy, noninvasive technique Continue reading >>

Mitochondrial Diabetes

Mitochondrial Diabetes

Around 1% of all cases of diabetes are due to mutations in the mitochondrial DNA (mtDNA). The commonest mutation is the m.3243A>G, associated with the maternally inherited diabetes and deafness (MIDD) syndrome. Patients with MIDD are often misclassified as type 2 or type 1 diabetes by physicians unaware of the syndrome. The presence of diabetes, deafness and a family history of the above in maternal relatives should raise suspicion of MIDD and genetic testing should be pursued in view of the implications for personalised management and genetic counselling for patients and relatives. Diabetes is treated initially with oral hypoglycaemics, but early use of insulin is commonly needed due to insulin deficiency. Maternally inherited diabetes and deafness (MIID/; MIM no. 520000) is a rare form of diabetes, accounting for approximately 1% of all diabetes cases [1] , first described in 1992 by van den Ouweland et al in a Dutch family and by Reardon et al in a UK family [2] [3] . This quite heterogeneous syndrome results from an A to G substitution at the conserved position 3243 (m.3243A>G) of the mitochondrial DNA. The age and the mode of presentation of diabetes result in this entity being often misdiagnosed as either T1D or T2D. The presence of diabetes and sensorineural deafness in a patient with family history of similar problems in maternal relatives should raise suspicion of MIDD. However, a number of other features may co-exist (see below). The clinical characteristics of diabetes can be similar to either T1D or T2D depending on the degree of insulinopenia. The presentation is usually insidious as in T2D, however around 20% of cases present acutely, even with ketoacidosis in a small proportion. Interestingly, in the vast majority of MIDD patients there is lack of autoim Continue reading >>

Diabetes Mellitus And Deafness

Diabetes Mellitus And Deafness

Diabetes mellitus and deafness (DAD) or maternally inherited diabetes and deafness (MIDD) is a subtype of diabetes which is caused from a point mutation at position 3243 in human mitochondrial DNA, which consists of a circular genome. This affects the gene encoding tRNALeu.[1][2] Because mitochondrial DNA is contributed to the embryo by the oocyte and not by spermatozoa, this disease is inherited from maternal family members only.[1] As indicated by the name, MIDD is characterized by diabetes and sensorineural hearing loss.[1] Signs and symptoms[edit] As suggested by the name, MIDD patients are subject to sensorineural hearing loss.[1] This begins with a reduction in the perception of frequencies above approximately 5 kHz which progressively declines, over the years, to severe hearing loss at all frequencies.[1] The diabetes that accompanies the hearing loss can be similar to Type 1 diabetes or Type 2 diabetes; however, Type 1-like diabetes is the more common form of the two. MIDD has also been associated with a number of other issues including kidney dysfunction, gastrointestinal problems, and cardiomyopathy.[3] Genetics[edit] Penetrance and age of onset[edit] MIDD represents 1% of patients with diabetes. Over 85% of people that carry the mutation in mitochondrial DNA at position 3243 present symptoms of diabetes. The average age at which MIDD patients are typically diagnosed is 37 years old but has been seen to range anywhere between 11 years to 68 years old. Of these diabetic patients carrying the mitochondrial DNA mutation at position 3243, 75% experience sensorineural hearing loss.[1] In these cases, hearing loss normally appears before the onset of diabetes and is marked by a decrease in perception of high tone frequencies.[3] The associated hearing loss with diab Continue reading >>

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