Humans ; Kearns-Sayre Syndrome ; diagnosis ; genetics

Cognition ; physiology ; Disease Management ; Humans ; Kearns-Sayre Syndrome ; diagnosis ; physiopathology

Coenzyme Q therapy has been used to support metabolic derangements in patients with mitochondrial encephalomyopathies. Biochemical analysis of the living human brain can be performed by magnetic resonance spectroscopy (MRS). We report upon a KSS patient who was serially imaged with localized proton MRS to monitor the efficacy of CoQ treatment. A 17-year-old girl with KSS was serially imaged with localized proton MRS performed on a GE 1.5 T SIGNA MRI/MRS system. The elevated lactate contents of lesions decreased after one month of CoQ therapy but were re-elevated 10 months after treatment. We conclude that MRS presents us with a powerful tool for monitoring the effects of therapeutic trials in mitochondrial encephalomyopathies.
Adolescence ; Brain/metabolism ; Brain/drug effects ; Case Report ; Female ; Human ; Kearns Syndrome/metabolism* ; Kearns Syndrome/drug therapy* ; Kearns Syndrome/diagnosis ; Lactic Acid/metabolism ; Magnetic Resonance Spectroscopy/diagnostic use* ; Pyruvic Acid/metabolism* ; Treatment Outcome ; Ubiquinone/therapeutic use*

Cognition ; physiology ; DNA, Mitochondrial ; genetics ; Genetic Testing ; Humans ; Kearns-Sayre Syndrome ; diagnosis ; genetics ; physiopathology ; Point Mutation ; genetics

BACKGROUNDKearns-Sayre syndrome (KSS) is a mitochondrial DNA (mtDNA) deletion disorder characterized by a triad of onset before 20 years of age, ophthalmoplegia, and pigmentary retinopathy. The heart and central nervous system are commonly involved. We summarized clinical and brain magnetic resonance imaging (MRI) features of a cohort of Chinese KSS patients.

METHODSNineteen patients confirmed by muscle biopsy and mtDNA analysis were enrolled. We examined clinical profiles, mainly focusing on changes in electrocardiogram (ECG) and brain MRI. The correlation between genotype and phenotype was statistically analyzed.

RESULTSThe mean age of onset was 9.6 ± 4.3 years, with all developing the classic triad at the time of diagnosis. Heart conduction block was detected in 63.2%, with four initially presenting as bundle branch block and developing into complete atrioventricular block over 3-72 months. Brain MRI showed symmetric high-T2 signals in 100% of cerebral and cerebellar white matter, as well as brainstem, 46.7% of basal ganglia, and 53.3% of thalamus. There were two patterns of cerebral white matter involvements, one with selective subcortical U-fibers and the other with periventricular white matter. The size of mtDNA deletion did not significantly correlate with age of onset or percentage of ragged blue fibers on muscle pathology.

CONCLUSIONSThe clinical features of KSS evolve dynamically, affecting the cardiac conduction system predominantly, highlighting the significance of ECG monitoring. Brain MRI showed changes involving both the white matter and deep gray nuclei. Clinical presentation or severity of muscle pathological changes is not related to the size of mtDNA deletions.

Adolescent ; Brain ; pathology ; physiology ; Child ; Child, Preschool ; DNA, Mitochondrial ; genetics ; Female ; Genotype ; Heart Block ; diagnosis ; genetics ; physiopathology ; Humans ; Kearns-Sayre Syndrome ; diagnosis ; genetics ; physiopathology ; Magnetic Resonance Imaging ; methods ; Male

PURPOSE: To evaluate the classification, diagnosis, and natural course of ophthalmoplegia associated with mitochondrial disease. MATERIALS AND METHODS: Among 372 patients with mitochondrial disease who visited our hospital between January 2006 and January 2016, 21 patients with ophthalmoplegia were retrospectively identified. Inclusion criteria included onset before 20 years of age, pigmentary retinopathy, and cardiac involvement. The 16 patients who were finally included in the study were divided into three groups according to disease type: Kearns-Sayre syndrome (KSS), KSS-like, and chronic progressive external ophthalmoplegia (CPEO). RESULTS: The prevalences of clinical findings were as follows: ptosis and retinopathy, both over 80%; myopathy, including extraocular muscles, 75%; lactic acidosis, 71%; and elevated levels of serum creatine kinase, 47%. Half of the patients had normal magnetic resonance imaging findings. A biochemical enzyme assay revealed mitochondrial respiratory chain complex I defect as the most common (50%). The prevalence of abnormal muscle findings in light or electron microscopic examinations was 50% each, while that of large-scale mitochondrial DNA (mtDNA) deletions in a gene study was 25%. We compared the KSS and KSS-like groups with the CPEO patient group, which showed pigmentary retinopathy (p < 0.001), cardiac conduction disease (p=0.013), and large-scale mtDNA deletions (p=0.038). KSS and KSS-like groups also had gastrointestinal tract disorders such as abnormal gastrointestinal motility (p=0.013) unlike the CPEO group. CONCLUSION: Patients with KSS had gastrointestinal symptoms, which may indicate another aspect of systemic involvement. The presence of large-scale mtDNA deletions was an objective diagnostic factor for KSS and a gene study may be helpful for evaluating patients with KSS.
Acidosis, Lactic ; Classification ; Creatine Kinase ; Diagnosis ; DNA, Mitochondrial ; Electron Transport ; Enzyme Assays ; Gastrointestinal Motility ; Gastrointestinal Tract ; Genes, vif ; Humans ; Kearns-Sayre Syndrome ; Magnetic Resonance Imaging ; Mitochondrial Diseases* ; Muscles ; Muscular Diseases ; Ophthalmoplegia* ; Ophthalmoplegia, Chronic Progressive External ; Prevalence ; Retinitis Pigmentosa ; Retrospective Studies

Mitochondrial cytopathies represent a heterogeneous group of multisystem disorder that preferentially affects the muscle and nervous systems. Mitochondrial respiratory chain enzyme complexes (MRC) defect can be the cause of many unexplained neurological disorders including epilepsy, cerebral palsy, delayed development and hypotonia. We retrospectively reviewed clinical and laboratory features of 16 patients who showed defects in MRC activity, confirmed by biochemical assay from spectrophotometry in muscles to characterize clinical and laboratory features for MRC defects and provide more precise diagnosis and effective treatments. In the patients with uncontrolled seizure activity, developmental regression, characteristic features of bilateral symmetric high signal intensity at deep nucleus and/or white matter in T2WI, the mitochondrial cytopathies should be added to the list of differential diagnoses. And lactate elevation in magnetic resonance spectroscopy (MRS) can be useful in the diagnosis of mitochondrial cytopathies.
Cerebral Palsy ; Child ; Diagnosis, Differential ; Electron Transport ; Epilepsy ; Humans ; Kearns-Sayre Syndrome ; Lactic Acid ; Magnetic Resonance Spectroscopy ; Mitochondrial Myopathies ; Muscle Hypotonia ; Muscles ; Nervous System ; Nervous System Diseases ; Retrospective Studies ; Seizures ; Spectrophotometry