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Query: UMLS:C0751651 (mitochondrial disease)
 1,844 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1958, Kearns and Sayre described a multisystem entity, now known as Kearns-Sayre syndrome (KSS). The syndrome is defined as exhibiting a triad of thus far unexplained degenerative conditions: progressive external ophthalmoplegia, retinal pigmentary degeneration, and heart block. Commonly accompanying findings include cerebellar dysfunction and CSF protein levels above 100 mg/dl. Symptoms usually appear in early childhood, but the onset has been seen occasionally in young adults. KSS is a mitochondrial disorder that occurs rarely; the actual incidence is unknown. Ocular findings consist of bilateral ptosis, chronic progressive external ophthalmoplegia, and pigmentary retinopathy. Corneal clouding and optic neuritis are infrequent. We herein report a classic case of Kearns Sayre syndrome and discuss the findings.
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PMID:Kearns-Sayre syndrome: a case report and review. 163 60

This study was aimed at investigating the value of MRI in the diagnosis of multiple sclerosis. In the Multiple Sclerosis Center of our University, we sorted out of the patients submitted to CSF and MR examinations, only those with clinically unquestionable multiple sclerosis, white matter abnormalities at MRI and normal CSF examination. These 21 patients were submitted to CSF and MRI examinations which were repeated whenever required if image quality was technically suboptimal; a variety of screening tests for different diseases mimicking multiple sclerosis were also performed. In 4 patients with white matter abnormalities at MRI which were considered atypical for multiple sclerosis, at image rereading and after laboratory tests the diagnosis were: coagulopathy, sarcoidosis, vasculitis and CNS lymphoma. In 2 cases with questionable white matter abnormalities at MRI, the final diagnosis were borreliosis and vasculitis. The remaining 15 patients had a diagnosis of multiple sclerosis in all but 3 cases in which subsequent clinical and laboratory examinations demonstrated the presence of vasculitis, embolism from interatrial septal aneurysm and mitochondrial disease. Our study suggests that in the patients with clinical findings of multiple sclerosis and disseminated MR lesions mimicking multiple sclerosis, but no CSF abnormalities, the classical clinical criteria may not be sufficiently specific and other diagnoses must therefore be excluded before making an "unquestionable" diagnosis of multiple sclerosis.
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PMID:[Multiple sclerosis with negative cerebrospinal fluid. Magnetic resonance differential diagnosis]. 787 31

We report values for CSF and blood lactate and acid-base balance in 8 girls with the Rett syndrome and correlate the findings with respiratory dysfunction. Three patients had elevated CSF lactate values; their hyperventilation (HV) was so intensive that the acid-base balance showed respiratory alkalosis with an abnormally low base excess. One of these three patients had normal CSF lactate and acid-base balance before she developed HV. Two patients were so young that they had not yet developed HV and their CSF lactate values were normal. One patient had elevated CSF lactate when she was younger and her HV was more intensive, but now her CSF and blood lactate were normal; her acid-base balance showed mild hypocapnia but was otherwise normal. Thus, in the Rett syndrome, CSF lactate elevation seems to be a secondary phenomenon connected with the intensive HV and alkalosis rather than a sign of any mitochondrial disorder.
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PMID:Elevated CSF lactate in the Rett syndrome: cause or consequence? 789 61

Typical cases of MELAS present a combination of clinical and neuroradiological features, lactacidaemia, and ragged red fibers (RRFs) in striated muscle. We have observed a MELAS-like syndrome in monozygotic twins. They developed seizures typically in conjunction with physical exertion, sleep deprivation or febrile episodes. Stroke-like episodes occurred usually during seizures. In twin 2 the course was fatal at age 20 years. Neuroradiological findings were typical of MELAS. Plasma lactate was normal in both. CSF lactate was normal in twin 1 and normal/elevated in twin 2. RRFs were not seen in muscle biopsies of the twins. Complex I activity was reduced in muscle in twin 1. Brain tissue removed at epilepsy surgery in twin 2 showed the presence of mitochondrial angiopathy. The commonest mitochondrial DNA mutation in MELAS, at base pair 3243, was absent. Lactacidaemia and mitochondrial myopathy with RRFs constitute part of the diagnostic criteria of MELAS. However, the absence of these features does not exclude mitochondrial disorder with the serious manifestations of MELAS (seizures and stroke-like episodes) as seen in these twins.
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PMID:Monozygotic twins with MELAS-like syndrome lacking ragged red fibers and lactacidaemia. 893 33

The authors report a child with a spinal muscular atrophy (SMA)-like picture, cardiomyopathy, and cytochrome c oxidase (COX) deficiency. Electromyography and muscle biopsy showed findings typical of SMA. However, COX staining of the muscle was negative. DNA analysis did not detect deletions in the survival motor neuron (SMN) gene. The lactate and lactate-to-pyruvate ratios were increased in blood and CSF. COX activity was decreased in muscle and fibroblasts. Western blot analysis showed reduced contents for all COX subunits. Patients with clinical features resembling SMA but with an intact SMN gene should be screened for a mitochondrial disorder.
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PMID:Spinal muscular atrophy-like picture, cardiomyopathy, and cytochrome c oxidase deficiency. 993 61

An Argentine male child died at 4.5 years of age of a lethal mitochondrial disease associated with a MELAS mutation and a Barth syndrome-like presentation. The child had severe failure to thrive from the early months and for approximately two years thereafter. In addition, the patient had severely delayed gross motor milestones, marked muscle weakness, and dilated cardiomyopathy that progressed to congestive heart failure. He also had persistently elevated urinary levels of 3-methylglutaconic and 2-ethylhydracrylic acids and low blood levels of cholesterol. Detailed histopathologic evaluation of the skeletal muscle biopsy showed high activity of succinate dehydrogenase, a generalized decrease of COX activity, and abundant ragged-red fibers. Electron microscopic studies revealed multiple mitochondrial abnormalities in lymphocytes and monocytes, in the striated muscle, and in the postmortem samples (muscle, heart, liver, and brain). Biochemical analysis showed a pronounced and constant lactic acidosis, and abnormal urinary organic acid excretion (unchanged in the fasting and postprandial states). In addition, in CSF there was a marked increase of lactate and beta-hydroxybutyrate (beta-HOB) and also a high systemic ratio beta-HOB/acetoacetate. Enzymatic assay of the respiratory chain in biopsied muscle showed 10% of complex I activity and 24% of complex IV activity compared with controls. Molecular studies of the mitochondrial genome revealed an A to G mutation at nucleotide pair 3243 in mitochondrial DNA, a well-known pathogenetic mutation (MELAS mutation) in all the patient's tissues and also in the blood specimens of the probands mother and sibs (4 of 5). The diagnosis of MELAS mutation was reinforced by the absence of an identifiable mutation in the X-linked G4.5 gene of the propositus. The present observation gives additional evidence of the variable clinical expression of mtDNA mutations in humans and demonstrates that all clinical variants deserve adequate investigation to establish a primary defect. It also suggests adding Barth-like syndrome to the list of phenotypes with the MELAS mutation.
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PMID:Barth's syndrome-like disorder: a new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation). 1124 64

Kearns-Sayre syndrome (KSS) is a multisystem mitochondrial disorder characterized by the invariant triad: onset before 20, progressive external ophthalmoplegia and pigmentary retinal degeneration, plus at least one of the following: complete heart block, cerebellar dysfunction and CSF protein >100 mg/dl. Autopsies from patients with KSS revealed widespread tissue distribution of mitochondrial (mt) DNA deletions. These deletions result in significantly lower activities of the enzymes of the respiratory chain. KSS has been associated with a variety of endocrine and metabolic disorders in <10% of patients, while renal tubular involvement is extremely rare. We present an 18-year-old girl with KSS who developed hypoparathyroidism and renal tubular dysfunction with inappropriate mangesiuria and kaliuria. We further discuss the renal tubular damage in KSS emphasizing its pathophysiology and clinical phenotype, and review the possible mechanisms of hypoparathyroidism in KSS.
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PMID:Severe hypomagnesemia and hypoparathyroidism in Kearns-Sayre syndrome. 1135 24

Mitochondrial dysfunction should be considered in the differential diagnosis of any progressive multisystem disorder. The diagnosis is most challenging when only one symptom is present. In contrast, the diagnosis is easier to consider when two or more seemingly unrelated symptoms are present, involving more than one organ system. It is important to consider the diagnosis of a mitochondrial disorder when dealing with an unexplained association of symptoms, with an early onset and progressive course involving seemingly unrelated organs. The investigation can be relatively straightforward if a person has a recognizable phenotype and if it is possible to identify a known pathogenic mtDNA mutation. The difficulty arises when no known mtDNA defect can be found or when the clinical abnormalities are complex and not easily matched to those of more common mitochondrial disorders. In summary: A full mitochondrial evaluation often is warranted in children with a complex neurologic picture or a single neurologic symptom and other system involvement. When the presentation is classic for a maternally inherited mitochondrial syndrome, such as MELAS, MERRF, or Leber's hereditary optic neuropathy, appropriate mtDNA studies should be obtained first. When the clinical picture is classic for a nuclear DNA inherited syndrome and the gene or linkage is known, such as MNGIE, the clinician should proceed with genetic studies. When the clinical picture is nonspecific but highly suggestive of a mitochondrial disorder, the clinician should start with plasma or CSF lactic acid, ketone bodies, plasma acylcarnitines, and urinary organic acids. If these studies are abnormal, the clinician should proceed with muscle biopsy and assessment of the respiratory chain enzymes. Normal plasma or CSF lactic acid does not rule out a mitochondrial disorder.
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PMID:Diagnosis and management of mitochondrial diseases. 1182 5

Kearns-Sayre syndrome (KSS) is a multisystem mitochondrial disorder characterized by the invariant triad: onset before 20, progressive external ophthalmoplegia and pigmentary retinal degeneration, plus at least one of the following: complete (or not) heart block, cereberal dysfunction and CSF protein above 100 mg/dl. Autopsies from patients with KSS revealed widespread tissue distribution mtDNA deletions. These deletions result in significantly lower activities of the enzymes of the respiratory chain. The same deletion of mitochondrial DNA present in skeletal muscle is found in myocardial tissue. An 18-year-old girl diagnosed with the KSS was admitted to our hospital because of an upper respiratory tract infection and dysphagia. ECG showed cardiac conduction defects. The patient had no history of syncope. At her surface ECG there was a complete RBBB (QRS duration approximately 130 ms), a clockwise rotation with an axis of approximately 90 degrees and a slight QT prolongation (420 ms). Echocardiography showed prolapse with thickening and degeneration of both mitral valve leaflets but without mitral regurgitation. The patient was started on a diet rich in potassium and pharmaceutical therapy with magnesium oxide (240 mg of elemental Mg p.o. per day), 1 g of calcium carbonate t.i.d., vitamin D (calcitriol 0.25 microg p.o. per day) and coenzyme Q(10) 100 mg daily and discharged 6 days later with slightly improved biochemical profile but apparent clinical improvement. Urgent pacemaker implantation was decided but unfortunately the patient died due to acute cardiac arrest 10 days later.
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PMID:Alarming atrioventricular block and mitral valve prolapse in the Kearns-Sayre syndrome. 1200 93

Alpers-Huttenlocher syndrome, considered a mitochondrial disease, combines encephalopathy and liver failure. An 11-year-old boy with Alpers-Huttenlocher syndrome underwent conventional MR imaging, diffusion-weighted imaging, and proton MR spectroscopy. Diffusion-weighted imaging showed cytotoxic edema interpreted as acute-phase encephalopathy. MR spectroscopy revealed a lactate peak in the cortex that appeared abnormal on diffusion-weighted images, possibly representing respiratory deficiency with anaerobic metabolism. MR spectroscopy proved to be more sensitive regarding lactate detection than did neurometabolic examination of serum and CSF. A reduced N-acetylaspartate-creatine ratio was detected in both the cortex that appeared abnormal and the cortex that appeared normal on the diffusion-weighted images, indicating neuronal damage that was widespread, even beyond the boundaries of conventional MR imaging changes.
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PMID:MR spectroscopic findings in a case of Alpers-Huttenlocher syndrome. 1222 90


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