Late-onset cerebellar ataxia with hypogonadism and muscle coenzyme Q10 deficiency.

Two brothers had late-onset progressive ataxia, cerebellar atrophy, and hypergonadotropic hypogonadism associated with coenzyme Q10 (CoQ10) deficiency in skeletal muscle. Both patients improved on high-dose CoQ10 supplementation, stressing the importance of CoQ10 deficiency in the differential diagnosis of cerebellar ataxia, even when onset is late.

Electrophysiological analysis of cognitive slowing in subjects with mitochondrial encephalomyopathy.

Mitochondrial encephalomyopathies (MEs) are multisystemic inherited disorders affecting tissues with high energy requirement such as the muscle, retina and central nervous system. Progressive external ophthalmoplegia and myopathy are the most common features in adults, and cognitive impairment is rare. In many neurodegenerative disorders, ERPs have been effectively performed to record cognitive slowing on tasks with different amount of information. To analyze the evidence for possible cognitive slowing, a standard auditory oddball paradigm with a button-press response was applied. Participants were 11 non-demented patients affected by mitochondrial encephalomyopathy and 14 age-matched normal controls. This hypothesis was tested using two tasks of different difficulty (pure tone vs. phonetic stimuli). Reaction time (RT), performance (P) and event-related potentials (ERPs) were measured. RT and P were not significantly different between the groups. Patients showed significantly increased N2 latency and reduced P3 amplitude on both tasks. No difference was found in pure tone and phonetic task conditions. Results were interpreted as electrophysiological signs of cognitive slowing--particularly in relation to stimulus evaluation--irrespective of sensory problems, response selection and cognitive load. These findings suggest that in ME patients, there may be a possible dysfunction of neural mechanisms underlying cognitive events and ERP generation.

Muscle phosphoglycerate mutase (PGAM) deficiency in the first Caucasian patient: biochemistry, muscle culture and 31P-MR spectroscopy.

Muscle phosphoglycerate mutase (PGAM) deficiency has been so far identified in only six patients, five of these being African Americans. We report the results of clinical, morphological, biochemical, muscle culture and 31P-MR spectroscopy studies in the first Caucasian patient with muscle PGAM deficiency. A 23-year-old man had a 10-year history of cramps after physical exertion with one episode of pigmenturia. Neurological examination and EMG study were normal. ECG and echocardiography revealed hypertrophy of the interventricular septum and slight dilation of the left chambers of the heart. Muscle biopsy revealed increased glycogen content and some accumulation of mitochondria. Muscle PGAM activity was markedly decreased (6.5% and 9.7% of control value in two different biopsies). Citrate synthase and other mitochondrial respiratory chain enzyme activities were much higher than normal. In contrast to the marked decrease of PGAM activity observed in muscle biopsy, total enzyme activity in the patient's aneural muscle culture was normal, being represented exclusively by BB isoenzyme. The deficiency of PGAM-MM isoenzyme was reproduced in the patient's innervated muscle culture. Muscle 31P-MR spectroscopy showed accumulation of phosphomonoesters only on fast "glycolytic" exercise. On "aerobic" exercise, Vmax, calculated from the work-energy cost transfer function, showed an increase consistent with the morphological and biochemical evidence of mitochondrial proliferation. This might represent a sort of compensatory aerobic effort in an attempt to restore muscle power.

Leber's hereditary optic neuropathy: genetic, biochemical, and phosphorus magnetic resonance spectroscopy study in an Italian family.

Three siblings of a family affected with Leber's hereditary optic neuropathy (LHON) showed a mitochondrial DNA mutation at position 11778. The lactate response to a standardized effort was increased in only one case. Muscle biopsies and biochemistry of muscle and platelet mitochondrial enzymes were normal. All patients showed an altered energy metabolism during exercise and during recovery after exercise on phosphorus 31-magnetic resonance spectroscopy (31P-MRS) of muscle. Brain 31P-MRS showed a decreased energy reserve (decreased PCr/Pi ratio) in all patients. 31P-MRS noninvasively demonstrated an altered mitochondrial energy metabolism in muscle and, for the first time, in the brains of LHON patients.

Muscle mitochondrial DNA deletion and 31P-NMR spectroscopy alterations in a migraine patient.

A 40-year-old female suffering from recurrent migrainous strokes is reported. She did not show any muscle weakness or wasting. Ragged red and cytochrome c oxidase negative fibers were present in the muscle biopsy. Muscle mitochondrial DNA analysis showed a 5 kb deletion, without a point mutation at nucleotide pair 3243 in the mitochondrial tRNALeu(UUR) gene. Phosphorus nuclear magnetic resonance spectroscopy of brain and gastrocnemius muscle showed a defective energy metabolism in both organs. An increased inorganic phosphate to phosphocreatine ratio due to a decreased phosphocreatine content was found in the occipital lobes, while an abnormal work-energy cost transfer function and a low rate of phosphocreatine post-exercise recovery were found in the muscle.