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Summary Mitochondrial DNA（mtDNA） deletion is a rare occurrence that results in defects to oxidative phosphorylation. The common clinical presentations of mtDNA deletion vary but include mitochondrial myopathy, Pearson syndrome, Kearns-Sayre syndrome, and progressive external ophthalmoplegia. However, in clinical practice, some cases cannot be classified as any typical syndrome due to the absence or overlap of phenotypes. Here, we report one case of a 5-year-old girl who presented with progressive deterioration of her clinical status, which included systemic electrolyte disturbance, Fanconi syndrome and sensorineural hearing loss. Through a combination of systematic examinations and molecular analyses, mitochondrial disease was confirmed. A novel 6991-base pair deletion（deletion of mtDNA nt 7808-14798） was identified which confirmed molecular pathogeny of patient. Following treatment, the patient was stabilized and her hearing loss improved by hearing aid. This paper provided an important reference for the diagnosis and treatment of similar patients in clinical practice., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Mitochondrial cytopathies include a heterogeneous group of diseases that are characterized by impaired oxidative phosphorylation. Current evidence suggests that renal involvement is probably more frequent than originally suspected but remains subclinical in a significant number of patients or is underestimated due to the severity of other clinical manifestations. Until recently, these diseases were thought to develop primarily in pediatric patients but patients that become symptomatic only in adulthood are now well recognized. From a renal standpoint, many patients with severe systemic disease and several patients with oligo-symptomatic clinical pictures have tubular defects, ranging from isolated tubular wasting of electrolytes to complete forms of renal Fanconi syndrome. Aside from rare cases of tubulo-interstitial and cystic diseases, other patients present with glomerular diseases that correspond in the majority of cases to focal segmental glomerulosclerosis lesions. Two specific entities should be singled out, namely the 3243 A>G mutation in the gene encoding for the mitochondrial leucine tRNA because it represents the most frequent form of mitochondrial glomerulopathy, and defects in the biosynthesis of coenzyme Q10 because they represent one of the few treatable forms of mitochondrial cytopathies., (Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Mitochondrial DNA (mtDNA) deletion is a rare occurrence that results in defects to oxidative phosphorylation. The common clinical presentations of mtDNA deletion vary but include mitochondrial myopathy, Pearson syndrome, Kearns-Sayre syndrome, and progressive external ophthalmoplegia. Here, we report the case of a 10-year-old boy who presented with progressive deterioration of his clinical status (which included hypoglycemia, short stature, sensorineural hearing loss, retinitis pigmentosa, and chronic gastrointestinal dysmotility) that progressed to acute deterioration with pancreatitis, Fanconi syndrome, lactic acidosis, and acute encephalopathy. Following treatment, the patient was stabilized and his neurological condition improved. Through a combination of histological examinations and biochemical and molecular analyses, mitochondrial disease was confirmed. A novel 3670-base pair deletion (deletion of mtDNA nt 7,628-11,297) was identified in the muscle tissue. A direct repeat of CTACT at the breakpoints was also detected., (Copyright © 2012. Published by Elsevier B.V.)

Background: Mitochondrial cytopathies are a diverse group of disorders characterized by impaired mitochondrial energy production. Disease manifestations are protean and may include seemingly disparate findings., Case Diagnosis/treatment: Here we report a 5-year-old girl with the uncommon pairing of bilateral corneal dystrophy requiring corneal transplantation and severe Fanconi syndrome recalcitrant to oral bicarbonate therapy necessitating intravenous supplementation. Etiological work-up included qualitative urine organic acid testing, which demonstrated abnormalities in lactate, pyruvate, and ketoacids suggestive of a mitochondrial etiology. Confirmatory genetic testing in blood leukocytes revealed a large, novel, heteroplasmic, de novo mitochondrial DNA deletion at nt 8648-16072., Conclusion: The finding of Fanconi syndrome with disease processes in other, seemingly unrelated, organ systems should raise clinical suspicion for mitochondrial disease. Early assessment of urine organic acids in the etiological work-up of Fanconi syndrome may assist in the identification of respiratory chain disorders.

Background: We report a patient with a highly unusual presentation of a mitochondrial disorder., History and Signs: An 8-year old girl presented with muscular cramps as well as height and weight deceleration. Investigations revealed lactic acidosis, electrolytic imbalance and urinary loss of glucose and electrolytes secondary to proximal renal tubulopathy consistent with Fanconi syndrome (FS). Ophthalmic examination revealed asymptomatic retinitis pigmentosa (RP) with no other ocular manifestations. A mitochondriopathy was suspected and genetic analysis performed., Therapy and Outcome: Southern blotting documented a heteroplasmic mutation of mtDNA with deletion/duplication. Three discrete mitochondrial genomes were detected: normal; deletion of 6.7 kb and a deletion/duplication consisting of 1 normal and 1 deleted genome. The relative proportions varied considerably between tissues., Conclusions: The association of FS and RP combines features of Kearns-Sayre syndrome and Pearson marrow-pancreas syndrome, without being typical of either. This highly unusual clinical presentation emphasises the need for systemic investigation of patients with FS and further underlines the importance of mtDNA analysis in patients with unexpected associations of affected tissues.

We report a sporadic large-scale mitochondrial deletion in a paediatric patient with Fanconi's syndrome. Renal biopsy disclosed chronic interstitial nephritis. Ultrastructural examination of the renal tissue showed many giant atypical mitochondria. Histochemical stains revealed markedly reduced cytochrome c oxidase (COX). Genetic analysis disclosed a novel mitochondrial deletion of 7.3 kb in both peripheral blood and renal tissue. Mitochondrial diseases have heterogeneous clinical phenotypes; mutation analysis has proved to be an effective tool in confirming the diagnosis.

We report the molecular findings in a child presenting with sideroblastic anemia and proximal tubulopathy. Analysis of mitochondrial DNA (mtDNA) from fibroblasts showed the presence of a 3.3-kb single deletion in 50% of the genomes. This mutation is, unlike other previously reported deletions in tubulopathy patients, not flanked by direct repeat sequences but by palindrome sequences at the deletion breakpoints, suggesting an unusual mechanism for production of deletion. These findings further expand our knowledge of the syndrome of anemia and tubulopathy due to single deletions of mtDNA.

Six children are presented with an isolated complex III deficiency in muscle tissue. More specifically, oxidation rates and ATP+CrP production rates from both pyruvate and succinate as substrates and/or the activity of decylubiquinol:cytochrome c oxidoreductase were all markedly reduced. Complex III deficiency was also present in liver of two patients tested, but could not be demonstrated in cultured fibroblasts of four patients tested. Mitochondrial DNA, extracted from muscle, was analyzed; no deletions or common point mutations were found. Four patients presented with a multi-organ disorder. Among these patients three presented at neonatal age with neurological signs and lactate elevation in blood and CSF, of whom two had severe neonatal Fanconi syndrome. One child, aged seven years, had encephalomyopathy, ophthalmoplegia, retinopathy and Wolff-Parkinson-White syndrome. The remaining two patients exhibited myopathy only, within the first year of life. Thus, like in other respiratory chain disorders, patients with complex III deficiency may present at any age and show variable symptoms and outcome, ranging from neonatal death to failure to thrive only. Apparently there are no clinical findings which are specific for complex III deficiency.

Large-scale mitochondrial DNA deletion was found in a 5-year-old girl with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and Fanconi's syndrome. Muscle biopsy disclosed ragged-red fibers and cytochrome c oxidase negative fibers. Respiratory chain studies were normal. Southern blot analysis demonstrated a 10.5-Kb heteroplasmic deletion in both muscle and blood. Deleted genomes represented 40% of total mitochondrial DNA in muscle and 63% in blood. There was no evidence of point mutations characteristic of MELAS. We suggest that not only patients with progressive external ophthalmoplegia syndromes, but also those with defined syndromes [e.g., MELAS or myoclonic epilepsy and ragged-red fibers (MERRF)] without characteristic point mutations, be screened for mitochondrial DNA deletions.

We report a patient with Pearson syndrome with failure to thrive, exocrine pancreas insufficiency, growth hormone deficiency and severe tubular dysfunction. The patient had no signs of liver involvement. Normal respiratory chain enzyme activity was found in the lymphocytes, but a mitochondrial DNA deletion was demonstrated in lymphocytes and in the kidney. Polymerase chain reaction amplification and sequence analysis revealed the presence of the 4,977 base pair "common" deletion in the mitochondrial genome. Our findings support the view that tubulopathies of unknown origin may be related to mitochondrial respiratory chain deficiency.

We report a patient with a clinical picture consisting of small birth weight, connatal hypoplastic anaemia, vacuolised bone marrow precursors, failure to thrive, and, subsequently, by insulin-dependent diabetes, renal Fanconi syndrome, lactic acidosis, complex organic aciduria, and elevation of haemoglobin F and of adenosine deaminase activity. The clinical course was progressive and death occurred at age 19 months. A high proportion of mitochondrial (mt) DNA molecules with a deletion of nucleotides 9238 to 15575 were identified in several tissues; about half of the shortened mtDNA molecules were concatenated to form circular dimers. The clinical and laboratory findings support recent conclusions that Pearson syndrome is not confined to bone marrow and pancreas, as originally described, but is a multi-organ disorder associated with deletions in part of the mtDNA molecules. The tissue distribution and the relative proportions of the abnormal mtDNA molecules apparently determine the phenotype and clinical course.