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Posttransplant diabetes mellitus, presenile deafness, and myopathy are not commonly accompanied symptoms after kidney transplant. We report the case of a 48-year-old woman with diabetes mellitus, sensorineural hearing loss, and severe myopathy without neuropathy after deceased donor kidney transplant. ShehadamitochondrialDNApointmutation at position 3243 (A>G), and mitochondrial diseases such as maternally inherited diabetes deafness or mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodeswere suspected.Diabetes andother symptoms following kidney transplant can often be overlooked as complications of immunosuppressants taken after kidney transplant. However, in patients without a known cause of their symptoms, appropriate examinations and consultation for other diseases, including genetic diseases, should be considered.

Although type 1 diabetes mellitus and, to a lesser extent, type 2 diabetes mellitus, are the prevailing forms of diabetes in youth, atypical forms of diabetes are not uncommon and may require etiology-specific therapies. By some estimates, up to 6.5% of children with diabetes have monogenic forms. Mitochondrial diabetes and cystic fibrosis related diabetes are less common but often noted in the underlying disease. Atypical diabetes should be considered in patients with a known disorder associated with diabetes, aged less than 25 years with nonautoimmune diabetes and without typical characteristics of type 2 diabetes mellitus, and/or with comorbidities associated with atypical diabetes.

Diabetes diagnosed in adults is a highly heterogeneous disorder. It mostly consists of what is referred to as type 2 diabetes but also comprises other entities (i.e. different diseases), including latent autoimmune diabetes, late onset forms of monogenic diabetes and familial diabetes of the adulthood, which has recently been the source of new diabetogenes discovery. Notably, type 2 diabetes is itself heterogeneous as it includes subtypes with onset at the extremes of age and/or weight distributions characterized by different degree of hyperglycemia and cardiovascular risk as compared to common forms of type 2 diabetes occurring in middle-aged, overweight/obese individuals. Understanding whether these are different presentations of one, highly heterogeneous disease or separate nosological entities with different clinical trajectories and requiring different treatments is essential to effectively pursue the path of precision medicine.

Introduction. Considering the urgent need to optimize the methods for preventing diabetes mellitus, it is important to find the methods of early diagnosis of carbohydrate metabolism disorders that precede the manifestation of type 2 diabetes mellitus and to promote the method of self-monitoring of carbohydrate metabolism available in Ukraine and abroad for each family. In connection with the peculiarities of energy metabolism, the expediency of studying the pyruvate dehydrogenase activity of blood for the purpose of early diagnosis of diabetes mellitus is obvious. Aim. To identify the persons with a hereditary predisposition to type 2 diabetes mellitus (with mitochondrial diabetes) in the population of the Prykarpattya region using the assessment of carbohydrate metabolism. To recommend the use of a bloodless visual method of studying the total content of α-ketoacids in the urine. Materials and methods. Into the study there were involved 292 practically healthy residents of the Prykarpattya region (166 men and 126 women aged 6 to 80 years) in which the blood glucose level did not exceed 5.6 mmol (100.8 mg%). The state of carbohydrate metabolism was evaluated using pyruvate dehydrogenase and α-ketoglutarate dehydrogenase tests. The monitoring was performed by indicators of pyruvate dehydrogenase activity in blood of healthy persons in the range of 8.01-16.30 μcat/l, as well as the 2-hour α-ketoneuria (6.4-11.4 mg, p

Background: Mitochondrial DNA (mtDNA) A3243G mutation is one of the major causative factors of mitochondrial diabetes mellitus. We found that tissues from 2 of 142 diabetes mellitus patients showed extremely high levels of the mutation. Objective: To investigate the level of the mutation in each tissue and to find the relationship between the mutation level and clinical features of the patients. Methods: Patient 1 was a 51-year-old woman, diagnosed as having diabetes mellitus at the age of 17, and was admitted to hospital because of cerebral infarction. Patient 2 was an 82-year-old woman who was admitted because of respiratory failure. mtDNA A3243G levels were measured in tissues collected at autopsy. Results: In patient 1, mtDNA A3243G levels were found to vary among the tissues. The patient’s highest mtDNA A3243G value was 42% and the lowest value was 9%, whereas the level in most individuals is usually less than 1%. Although patient 2 did not exhibit serious clinical symptoms of diabetes mellitus, the mtDNA A3243G level was extremely high in all of the tissues surveyed (range 32–47%). Conclusion: Although both patients showed high levels of the mtDNA A3243G mutation, their clinical conditions differed greatly. Thus, mitochondrial diabetes mellitus patients may show a wide variety of clinical features and large variations in life span.

Diabetes mitocondrial é freqüentemente associado à mutação mitocondrial A3243G. A prevalência desse subtipo de diabetes na população diabética varia de 0,5 a 3%, dependendo do grupo populacional estudado. OBJETIVO: Examinar a freqüência e o quadro clínico do diabetes associado com a mutação mitocondrial A3243G em pacientes brasileiros com tolerância a glicose alterada. MÉTODOS: A população estudada foi composta por 78 indivíduos portadores de diabetes mellitus tipo 1 (grupo I), 148 diabéticos tipo 2 (grupo II), 15 diabéticos tipo 1 ou tipo 2 portadores de disacusia (grupo III) e 492 indivíduos da comunidade nipo-brasileira com vários graus de intolerância a glicose. O DNA foi extraído de leucócitos do sangue periférico e a mutação A3243G foi determinada através da amplificação por PCR e digestão por Apa 1. Em alguns pacientes, o DNA também foi extraído da mucosa oral e folículo capilar. A mutação A3243G foi identificada em três indivíduos, todos do grupo III, resultando em uma prevalência de 0,4%. Os carreadores da mutação apresentavam diagnóstico do diabetes em idade jovem, índice de massa corpórea normal ou baixo e requerimento de insulina. CONCLUSÃO: Diabetes mitocondrial é um subtipo raro de diabetes em nossa população e deve ser investigado naqueles indivíduos portadores de diabetes e surdez. Maternal inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial RNA Leu (UUR) at base pair 3243. The prevalence of MIDD in the diabetes population ranges between 0.5-3.0% depending on the ethnic background. AIM: To examine the frequency and clinical features of diabetes associated with this mutation in Brazilian patients with glucose intolerance. METHODS: The study population comprised: 78 type 1 diabetic subjects (group I), 148 patients with type 2 diabetes (group II), 15 patients with either type 1 or type 2 diabetes and hearing loss (group III) and 492 Japanese Brazilians with varying degrees of glucose intolerance. DNA was extracted from peripheral blood leucocytes and the A3243G mutation was determined by PCR amplification and Apa 1 digestion. In some individuals DNA was also extracted from buccal mucosa and hair follicles. The 3243 bp mutation was found in three individuals, all from group III, resulting in a prevalence of 0.4%. These subjects had an early age of diagnosis of diabetes, low or normal body mass index and requirement of insulin therapy. In conclusion MIDD is rare in our population and should be investigate in patients with diabetes and deafness.

ZusammenfassungGene spielen bei der Pathogenese des Diabetes mellitus eine wichtige Rolle. Die häufigste Form bei Kindern und Jugendlichen ist der Diabetes mellitus Typ 1. Bei vorhandener genetischer Prädisposition kann durch verschiedene Umweltfaktoren eine Autoimmunreaktion ausgelöst werden, welche durch Zerstörung der Betazellen zum Insulinmangel und somit zum Diabetes mellitus Typ 1 führt. Beim Diabetes mellitus Typ 2, welcher bei der zunehmenden Adipositas im Kindes- und Jugendalter in den letzten Jahren in Deutschland häufiger zu beobachten ist, spielen genetische Faktoren eine entscheidende Rolle. Der Diabetes mellitus Typ 2 wird polygen vererbt. Bisher liegen jedoch nur unzureichende Daten vor, um eine genetische Diagnostik in der Praxis sinnvoll erscheinen zu lassen. Bei einer Reihe von weiteren Diabetestypen ist deren genetische Ursache in den letzten Jahrzehnten geklärt worden. Eine genetische Diagnostik ist in diesen Fällen notwendig und sinnvoll. Der Maturity Onset Diabetes of the Young (MODY) fällt meist durch seine im Vergleich zum Diabetes mellitus Typ 1 mildere Verlaufsform auf und wird mit einer Häufigkeit von 5–10% aller Diabetesformen beziffert. Der MODY Typ 2 wird durch eine Mutation im Glukokinase-Gen hervorgerufen, der MODY Typ 3 durch eine Mutation im HNF-1α-Gen. Der mitochondriale Diabetes mellitus wird aufgrund der häufig auftretenden Schwerhörigkeit auch als MIDD (Maternally Inherited Diabetes and Deafness) bezeichnet und durch Mutationen im mitochondrialen Genom hervorgerufen. Weiterhin wurden in den letzten Jahren verschiedene Genmutationen beim sehr seltenen neonatalen Diabetes mellitus (transienter und permanenter neonataler Diabetes mellitus) aufgeklärt.

Background Mitochondrial diabetes is a kind of rare diabetes caused by monogenic mutation in mitochondia. The study aimed to summarize the clinical phenotype profiles in mitochondrial diabetes withm.3243A>G mitochondrial DNA mutation and to investigate the mechanism in this kind of diabetes by analyzing the relationship among clinical phenotypes and peripheral leukocyte DNA telomere length. Methods Fifteen patients with maternally inherited diabetes in five families were confirmed as carrying the m.3243A>G mitochondrial DNA mutation. One hundred patients with type 2 diabetes and one hundred healthy control subjects were recruited to participate in the study. Sanger sequencing was used to detect the m.3243A>G mitochondrial DNA mutation. The peak height G/A ratio in the sequence diagram was calculated. Real-time polymerase chain reaction (PCR) was used to measure telomere length. Results The patients with mitochondrial diabetes all had definite maternally inherited history, normal BMI (19.5 ± 2.36 kg/m2), early onset of diabetes (35.0 ± 14.6 years) and deafness. The peak height G/A ratio correlated significantly and negatively with the age at onset of diabetes (≦25 years, 61.6 ± 20.17 %; 25–45 years, 16.59 ± 8.64 %; >45 years, 6.37 ± 0.59 %; p = 0.000). Telomere length was significantly shorter among patients with mitochondrial diabetes and type 2 diabetes than in the control group (1.28 ± 0.54 vs. 1.14 ± 0.43 vs. 1.63 ± 0.61; p = 0.000). However, there was no significant difference between patients with mitochondrial diabetes and those with type 2 diabetes. There was no correlation between telomere length and the peak height G/A ratio. Conclusion Deafness with definite maternal inheritance and normal BMI, associated with elevated blood lactic acid and encephalomyopathy, for the most part, suggest the diagnosis of mitochondrial diabetes . The peak height G/A ratio could reflect the spectrum of age at onset of the disease. Telomere length was shorter in patients with mitochondrial diabetes and those with type 2 diabetes, which suggests that the shorter telomere length is likely involved in the pathogenesis of diabetes but is not specific for this kind of diabetes.

Diabetes mellitus is an etiologically heterogeneous disorder. Monogenic forms of diabetes mellitus cover a heterogeneous group of diabetes which are uniformly caused by a single gene mutation and are characterized by impaired insulin secretion of the pancreatic beta cell. It is estimated that they account for up to 5% of all cases of diabetes mellitus, which are often not diagnosed or are misclassified as type 1 or 2 diabetes. However, accurate diagnosis is important because of the special implications for treatment, prognosis and family risk. The knowledge of typical clinical features such as mode of inheritance, age at diagnosis and impaired insulin secretion, as well as genetic testing establishes the diagnosis of MODY, mitochondrial diabetes and neonatal diabetes. In particular, diabetes occurring under 6 months of age—usually termed neonatal diabetes—appears to be predominantly monogenic.

Monogenic forms of diabetes mellitus cover a heterogeneous group of diabetes which are uniformly caused by a single gene mutation and are characterised by impaired insulin secretion of the pancreatic beta cell. It is estimated that they account for up to 5% of all cases of diabetes mellitus, which are often not diagnosed or are misclassified as type 1 or 2 diabetes. However, accurate diagnosis is important because of the special implications for treatment, prognosis and family risk. The knowledge of typical clinical features such as mode of inheritance, age at diagnosis and impaired insulin secretion, as well as genetic testing establishes the diagnosis of MODY, mitochondrial diabetes and neonatal diabetes.

West syndrome occurs in infancy and in early childhood. It is characterized by intractable seizures occurring almost daily, severe psychomotor retardation, poor prognosis and EEG abnormalities, known as hypsarrhythmia. We report here the case of a 28-year-old patient, who was diagnosed with West syndrome when he was 8 months old and with diabetes mellitus when he was 25 years old. Sequencing analyses and restriction analyses were suggestive of mitochondrial diabetes. Four years after the diagnosis of diabetes, this patient's diabetes is still controlled by diet and biguanides.

Cardiac involvement and its clinical course in a diabetic patient with a mitochondrial tRNALeu(UUR) mutation at position 3243 is reported in a 54-year-old man with no history of hypertension. At age 46, an electrocardiogram showed just T wave abnormalities. At age 49, it fulfilled SV1 + RV5 or 6 >35 mm with strain pattern. At age 52, echocardiography revealed definite left ventricular (LV) hypertrophy, and abnormally increased mitochondria were shown in biopsied endomyocardial specimens. He was diagnosed as having developed hypertrophic cardiomyopathy associated with the mutation. However, at age 54, SV1 and RV5,6 voltages were decreased, and echocardiography showed diffuse decreased LV wall motion and LV dilatation. Because he had mitochondrial diabetes, the patient's heart rapidly developed hypertrophic cardiomyopathy, and then it seemed to be changing to a dilated LV with systolic dysfunction. Rapid progression of cardiomyopathy can occur in mitochondrial diabetes. (Jpn Circ J 1999; 63: 130 - 132)

We previously reported the first identified case of mitochondrial diabetes caused by a T-to-C transition at position 3271 (1). At age 32 years, the patient had lower limb paresthesia. Since beginning diet therapy at age 33 years, his glycemic control has generally been good (HbA1c 6–7%) and the paresthesia has disappeared. During 12 years of follow-up, we observed two important clinical features: 1 ) lower limb …

In 1997, we reported the first identified case of mitochondrial diabetes caused by a T-to-C transition at position 3264 (1). The patient had type 2 diabetes, lipoma, facial palsy, ophthalmoplegia, and hearing loss. His unique profile suggests the heterogeneity of mitochondrial (mt)DNA-related diabetes. Among the characteristics, bilateral facial palsy and ophthalmoplegia (right eye) were noteworthy because they have not been reported in mitochondrial diabetes associated with other pathogenetic mutations. At age 59 years, facial palsy appeared first on the right side and 6 months later on the left side. It occurred without pain and became persistent. …