Primary mitochondrial disease as a rare cause of unclear breathlessness and distinctive performance degradation - a case report.

BACKGROUND: Primary muscular disorders (metabolic myopathies, including mitochondrial disorders) are a rare cause of dyspnea. We report a case of dyspnea caused by a mitochondrial disorder with a pattern of clinical findings that can be classified in the known pathologies of mitochondrial deletion syndrome. CASE PRESENTATION: The patient presented to us at 29 years of age, having had tachycardia, dyspnea, and functional impairment since childhood. She had been diagnosed with bronchial asthma and mild left ventricular hypertrophy and treated accordingly, but her symptoms had worsened. After more than 20 years of progressive physical and social limitations was a mitochondrial disease suspected in the exercise testing. We performed cardiopulmonary exercise testing (CPET) with right heart catheterization showed typical signs of mitochondrial myopathy. Genetic testing confirmed the presence of a ~ 13 kb deletion in mitochondrial DNA from the muscle. The patient was treated with dietary supplements for 1 year. In the course of time, the patient gave birth to a healthy child, which is developing normally. CONCLUSION: CPET and lung function data over 5 years demonstrated stable disease. We conclude that CPET and lung function analysis should be used consistently to evaluate the cause of dyspnea and for long-term observation.

Kickboxing a cardiomyopathy: mitochondrial sequencing provides answer for young athlete and her family.

Mitochondrial diseases are rare, often go undiagnosed and can lead to devastating cascades of multisystem organ dysfunction. This report of a young woman with hearing loss and gestational diabetes illustrates a novel presentation of a cardiomyopathy caused by a previously described mutation in a mitochondrial gene, MT-TL1. She initially had biventricular heart dysfunction and ventricular arrhythmia that ultimately recovered with beta blockade and time. She continues to participate in sport without decline. It is important to keep mitochondrial diseases in the differential diagnosis and understand the testing and management strategies in order to provide the best patient care.

Coenzyme Q10 deficiency in mitochondrial DNA depletion syndromes.

We evaluated coenzyme Q10 (CoQ) levels in patients studied under suspicion of mitochondrial DNA depletion syndromes (MDS) (n=39). CoQ levels were quantified by HPLC, and the percentage of mtDNA depletion by quantitative real-time PCR. A high percentage of MDS patients presented with CoQ deficiency as compared to other mitochondrial patients (Mann-Whitney-U test: p=0.001). Our findings suggest that MDS are frequently associated with CoQ deficiency, as a possible secondary consequence of disease pathophysiology. Assessment of muscle CoQ status seems advisable in MDS patients since the possibility of CoQ supplementation may then be considered as a candidate therapy.

Diagnosis and treatment of mitochondrial myopathies.

Mitochondrial disorders are a heterogeneous group of disorders resulting from primary dysfunction of the respiratory chain. Muscle tissue is highly metabolically active, and therefore myopathy is a common element of the clinical presentation of these disorders, although this may be overshadowed by central neurological features. This review is aimed at a general medical and neurologist readership and provides a clinical approach to the recognition, investigation, and treatment of mitochondrial myopathies. Emphasis is placed on practical management considerations while including some recent updates in the field.

Progression despite replacement of a myopathic form of coenzyme Q10 defect.

The authors report 7 years of follow-up evaluation of a patient with coenzyme Q10 (CoQ10) deficiency. Initial symptoms of exercise intolerance and hyperlactatemia improved markedly with substitutive treatment. However, CoQ(10) supplementation did not prevent the onset of a cerebellar syndrome. A switch to idebenone treatment resulted in clinical and metabolic worsening, which disappeared with subsequent CoQ10 treatment. CoQ10 defects may cause progressive neurologic disease despite supplementation.

Auditory neuropathy and a mitochondrial disorder in a child: case study.

A child was referred for an audiologic evaluation, to include auditory brainstem evoked response testing, due to inconsistent responses to sound and delayed speech and language development. Results were characteristic of auditory neuropathy. In view of subsequent decline in motor function, a genetics evaluation was conducted, revealing a mitochondrial disorder. A brief overview of mitochondrial genetics in association with hearing loss is presented. The patient's audiologic profile is described and the implications for management are discussed.

[Subconjunctival anesthesia: an alternative for vitrectomy in mitochondrial myopathy]. / Anestesia subconjuntival: una alternativa para la vitrectomía en la miopatía mitocondrial.

The case of a 63-year-old woman with mitochondrial myopathy with palpebral ptosis and nighttime nasal home oxygen therapy is reported. The patient successfully underwent outpatient vitrectomy with subconjunctival anesthesia, receiving no premedication or sedation during the operation. Subconjunctival analgesia was provided, with prior instillation of an anesthetic collyrium followed by subconjunctival injection of 1 ml of 0.4% bupivacaine and 2% lidocaine. Analgesia during surgery was satisfactory. We review the possibilities of using this technique in patients at high risk of presenting postoperative complications after general anesthesia, and discuss the possible side effects on musculature when peribulbar or retrobulbar anesthesia is provided.

Lipoic (thioctic) acid increases brain energy availability and skeletal muscle performance as shown by in vivo 31P-MRS in a patient with mitochondrial cytopathy.

A woman affected by chronic progressive external ophthalmoplegia and muscle mitochondrial DNA deletion was studied by phosphorus magnetic resonance spectroscopy (31P-MRS) prior to and after 1 and 7 months of treatment with oral lipoic acid. Before treatment a decreased phosphocreatine (PCr) content was found in the occipital lobes, accompanied by normal inorganic phosphate (Pi) level and cytosolic pH. Based on these findings, we found a high cytosolic adenosine diphosphate concentration [ADP] and high relative rate of energy metabolism together with a low phosphorylation potential. Muscle MRS showed an abnormal work-energy cost transfer function and a low rate of PCr recovery during the post-exercise period. All of these findings indicated a deficit of mitochondrial function in both brain and muscle. Treatment with 600 mg lipoic acid daily for 1 month resulted in a 55% increase of brain [PCr], 72% increase of phosphorylation potential, and a decrease of calculated [ADP] and rate of energy metabolism. After 7 months of treatment MRS data and mitochondrial function had improved further. Treatment with lipoate also led to a 64% increase in the initial slope of the work-energy cost transfer function in the working calf muscle and worsened the rate of PCr resynthesis during recovery. The patient reported subjective improvement of general conditions and muscle performance after therapy. Our results indicate that treatment with lipoate caused a relevant increase in levels of energy available in brain and skeletal muscle during exercise.