External ophthalmoplegia and ptosis are common manifestations of mitochondrial cytopathy, such as chronic progressive external ophthalmoplegia (CPEO). However, these symptoms and signs may also be presenting features of myasthenia gravis (MG). There are a few reports of CPEO with elevated acetylcholine receptor antibody (AchR-Ab). We report a case of AD-type CPEO with elevated acetylcholine receptor binding antibody. We confirmed a mutation on the SLC25A4 gene by molecular analysis.
Acetylcholine ; Kearns-Sayre Syndrome ; Mitochondrial Myopathies ; Myasthenia Gravis ; Ophthalmoplegia ; Ophthalmoplegia, Chronic Progressive External

Chronic progressive ophthalmoplegia(CPEO) is a vague clinical entity, which needs further understanding and there is still intense controversy about the classification on the Syndrome of Progressive External Ophthalmoplegia. In our country two cases of similar disease were reported with the title of oculocraniosomatic disease and CPEO with ragged red fiber. Authors experienced a 39 year-old woman with typical Kearns-Sayre syndrome(KSS) and a 44 year-old man with ophthalmoplegia plus syndrome. The case with Kearns-Sayre syndrome had an invariable triad of 1) chronic progressive external ophthalmoplegia and onset before 20 years of age, 2) retinal pigmentary degeneration of salt & pepper pattern and 3)mitochondrial abnormalities with additional findings of increased cerebrospinal fluid protein and cerebellar ataxia rhe other case with ophthalmoplegia plus with ragged red fiber syndrome had similar symptomatology to Kearns-Sayre syndrome except for typical retinal pigmentary degeneration. Both cases showed electromyographic myopathic findings and typical histopathologic features as ragged red fiber and paracrystalline mitochondrial aggregations. Therefore authors would say that these clinical different phenotypes of mitochondrial abnormality should be understood in detail by the biochemical investigations.
Adult ; Cerebellar Ataxia ; Cerebrospinal Fluid ; Classification ; Female ; Humans ; Kearns-Sayre Syndrome ; Ophthalmoplegia* ; Ophthalmoplegia, Chronic Progressive External ; Phenotype ; Retinaldehyde

OBJECTIVE

This study described the ophthalmic symptoms and signs in patients with nasopharyngeal carcinoma (NPCA).

This was a retrospective, cross-sectional, descriptive study involving patients with histologically-confirmed NPCA seen in two subspecialty eye clinics in a single referral hospital from January 2014 to December 2018. Chart review obtained data on symptoms and ophthalmic findings of patients with NPCA on the first visit. Descriptive statistics was used to analyze the data.

There were 36 patients in the study. There were 27 males (75%) and mean age was 47 years (Range: 13 - 83). Delay to consult was marked, with 28 patients (78%) presenting later than three months; 19 (53%) had invasion to distant sites on presentation. Almost all of the patients (35/36 or 97%) had either diplopia or blurring of vision, with nasal symptoms as the most common extra-ophthalmic accompanying symptom. Multiple cranial nerve palsies, particularly optic nerve plus at least one ocular motor nerve, was a prominent feature. The combination of nasal symptoms with ophthalmoparesis was noted in 24 patients (67%) and was identified as a red flag for NPCA.

Blurred vision and diplopia were the most common ocular complaints of patients with NPCA who were evaluated at the ophthalmology department of a tertiary hospital. Blurred vision is frequently from optic nerve involvement while diplopia is due to ophthalmoparesis secondary to multiple ocular motor cranial nerves involvement. Male patients in their 40s who present with combination of optic neuropathy or ocular motor palsies should be probed for presence of otologic or nasal symptoms as well as neck masses as these are the common presentation of NPCA in the ophthalmology clinics.

Blepharoptosis is a common indication for surgery in plastic surgery units, yet its possible underlying pathology frequently remains unidentified. A 52-year-old man with a 20-year history of progressive bilateral ptosis (right>left) presented with recurrent ptosis of both eyes; he had undergone an operation on the levator aponeurosis 12 years prior. Due to the suspicion of an underlying disease, he was evaluated further. Chronic progressive external ophthalmoplegia in transition to the more severe syndromic variant Kearns-Sayre syndrome, a mitochondrial disorder causing myopathy, was diagnosed. The patient was treated with coenzyme Q10, and he underwent ptosis surgery on both eyes. This case illustrates a potentially multi-systemic disease that was diagnosed by a further evaluation of a common symptom, in this case worsening blepharoptosis. Awareness of myopathic symptoms is necessary to prevent overlooking serious yet improvable conditions.
Blepharoplasty ; Blepharoptosis* ; Humans ; Kearns-Sayre Syndrome* ; Middle Aged ; Mitochondrial Diseases ; Muscular Diseases ; Ophthalmoplegia, Chronic Progressive External ; Pathology ; Surgery, Plastic

Kearns-Sayre Syndrome (KSS) is rare mitochondrial disorder characterized by chronic progressive external ophthalmoplegia, atypical retinal pigmentation and complete heart block. It is occasionally combined endocrinologic symptoms such as hypoparathyroidism, short stature, diabetes mellitus and hypothyroidism. We reported the effect of Coenzyme Q10 on total serum calcium concentration in 17 years old girl with KSS and hypoparathyroidism. The patients was treated with alfacalcidol (1alpha-OHD3), Coenzyme Q10 and oral calcium agent. Total serum calcium concentration had even remained within normal range and hypercalcemia was developed suddenly after treatment of combination of Coenzyme Q10 and alfacalcidol (1alpha-OHD3). After stop of all medication, her total calcium concentration was decreased to 7.6 mg/dL and remained in normal range with oral calcium (2 g/day) and Coenzyme Q10 (150 mcg/day) daily. The action of Coenzyme Q10 is not clearly defined but, we could explain Coenzyme Q10 activates the capacity of the patient to produce the active form of Vitamin D, 1alpha-OHD3.
Adolescent ; Calcium ; Diabetes Mellitus ; Female ; Heart Block ; Humans ; Hypercalcemia* ; Hypoparathyroidism* ; Hypothyroidism ; Kearns-Sayre Syndrome* ; Mitochondrial Diseases ; Ophthalmoplegia, Chronic Progressive External ; Pigmentation ; Reference Values ; Retinaldehyde ; Vitamin D

Kearns-Sayre syndrome (KSS) is a rare multisystem mitochondrial disorder associated with progressive external ophthalmoplegia, atypical pigmentary degeneration of the retina, and complete heart block. KSS can lead to a risk of sudden death because of the potential progression of conduction abnormalities such as right or left bundle branch block or complete atrioventricular (AV) block. Here we describe the case of a KSS patient with type I diabetes who experienced syncope in the presence of complete AV block, confirmed by muscular biopsy.
Atrioventricular Block* ; Biopsy ; Bundle-Branch Block ; Death, Sudden ; Heart Block ; Humans ; Kearns-Sayre Syndrome* ; Mitochondrial Diseases ; Ophthalmoplegia, Chronic Progressive External ; Retina ; Syncope

Serial Brain MRI was performed on a seventeen-year-old girl with Kearns-Sayre syndrome. At the age of 11, she complained bilateral ptosis. Two years later, bilateral blepharoplasty was done and brain MRI was taken. T2-weighted MRI sequence showed high signal intensity areas in the brainstem, thalamus and white matter of the cerebrum and cerebellum bilaterally. Four years later, chronic progressive external ophthalmoplegia developed and serial MRI and proton MRS were taken. Follow-up MRI showed similar but slightly progressed findings compared with previous films. The proton MR spectroscopic imaging demonstrated focal localization of abnormally increased lactate content in the involved area of the brain.
Blepharoplasty ; Brain ; Brain Stem ; Cerebellum ; Cerebrum ; Female ; Follow-Up Studies* ; Humans ; Kearns-Sayre Syndrome* ; Lactic Acid ; Magnetic Resonance Imaging* ; Magnetic Resonance Spectroscopy ; Ophthalmoplegia, Chronic Progressive External ; Protons ; Thalamus

PURPOSE: Chronic progressive external ophtahlmoplegia(CPEO) is a common phenotype of mitochondrial myopathy. CPEO has wide clinical spectrum with variable severity and can be divided into 3 groups; Kearns-Sayre syndrome, ophthalmoplegia plus and isolated CPEO. Single large-scale deletion, multiple deletions, point mutation of muscle mitochondrial DNA(mtDNA) and nuclear gene defect are associated with CPEO. We reviewed two cases of CPEO associated with the gene defect of mtDNA. METHODS: mtDNA was extracted from muscle biopsy tissue and blood leukocytes. We carried out polymerase chain reaction(PCR), restriction fragment length polymorphism (RFLP) assay and automated sequencing of the mtDNA. RESULTS: Case 1 presented with progressive external ophthalmoplegia, short stature, hypothyroidism and sensorineural hearing loss. A novel 7.6 kb-deletion was found in muscle and leukocyte mtDNA. Case 2 presented with isolated CPEO. A novel 6.2 kb- deletion was found in muscle mtDNA. CONCLUSION: We detected novel single large-scale deletion of mtDNA in 2 cases of CPEO with various clinical manifestations in our population. We have to investigate multi-organ involvement with regular follow-up for patients who present with progressive ophthalmoplegia
Biopsy ; DNA, Mitochondrial* ; Follow-Up Studies ; Hearing Loss, Sensorineural ; Humans ; Hypothyroidism ; Kearns-Sayre Syndrome ; Leukocytes ; Mitochondria ; Mitochondrial Myopathies ; Ophthalmoplegia ; Ophthalmoplegia, Chronic Progressive External* ; Phenotype ; Point Mutation ; Polymorphism, Restriction Fragment Length

PURPOSE: Chronic progressive external ophtahlmoplegia(CPEO) is a common phenotype of mitochondrial myopathy. CPEO has wide clinical spectrum with variable severity and can be divided into 3 groups; Kearns-Sayre syndrome, ophthalmoplegia plus and isolated CPEO. Single large-scale deletion, multiple deletions, point mutation of muscle mitochondrial DNA(mtDNA) and nuclear gene defect are associated with CPEO. We reviewed two cases of CPEO associated with the gene defect of mtDNA. METHODS: mtDNA was extracted from muscle biopsy tissue and blood leukocytes. We carried out polymerase chain reaction(PCR), restriction fragment length polymorphism (RFLP) assay and automated sequencing of the mtDNA. RESULTS: Case 1 presented with progressive external ophthalmoplegia, short stature, hypothyroidism and sensorineural hearing loss. A novel 7.6 kb-deletion was found in muscle and leukocyte mtDNA. Case 2 presented with isolated CPEO. A novel 6.2 kb- deletion was found in muscle mtDNA. CONCLUSION: We detected novel single large-scale deletion of mtDNA in 2 cases of CPEO with various clinical manifestations in our population. We have to investigate multi-organ involvement with regular follow-up for patients who present with progressive ophthalmoplegia
Biopsy ; DNA, Mitochondrial* ; Follow-Up Studies ; Hearing Loss, Sensorineural ; Humans ; Hypothyroidism ; Kearns-Sayre Syndrome ; Leukocytes ; Mitochondria ; Mitochondrial Myopathies ; Ophthalmoplegia ; Ophthalmoplegia, Chronic Progressive External* ; Phenotype ; Point Mutation ; Polymorphism, Restriction Fragment Length

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