Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 16-year-old girl presented with early-onset cerebellar ataxia, myoclonus, elevated lactic acidosis and hypogonadotropic hypogonadism. Muscle biopsy specimens revealed fibres with a "ragged" appearance with increased mitochondria and lipid droplets. Biochemical investigation revealed a deficiency of complex bc1 (complex III) of the mitochondrial respiratory chain. Genetic analysis did not show either deletions or known mutations of mitochondrial DNA (mtDNA). Phosphorus magnetic resonance spectroscopy (31P-MRS) showed defective energy metabolism in brain and gastrocnemius muscle. A decreased phosphocreatine (PCr) content was found in the occipital lobes accompanied by normal inorganic phosphate (Pi) and cytosolic pH. These findings represented evidence of a high cytosolic adenosine diphosphate concentration and a relatively high rate of metabolism accompanied by a low phosphorylation potential. Muscle 31P-MRS showed a high Pi content at rest, abnormal exercise transfer pattern and a low rate of PCr post-exercise recovery. These findings suggested a deficit of mitochondrial function. Therapy with vitamins K3 and C normalized brain 31P-MRS indices, whereas it did not affect muscle bioenergetic metabolism. In this patient, the endocrinological disorder is putatively due to a mitochondrial cytopathy. Although an unknown mtDNA mutation cannot be ruled out, the genetic defect may lie in the nuclear genome.
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PMID:Early-onset cerebellar ataxia, myoclonus and hypogonadism in a case of mitochondrial complex III deficiency treated with vitamins K3 and C. 779 18

We report a 23-year-old man with mitochondrial encephalomyopathy. At 21 years of age, he noted speech distubance. Since his dysarthria did not improve thereafter, he was admitted to our hospital. On admission, he showed mild gynecomastia. Neurological examination revealed mild decrease in performance IQ in WAIS-R, mild scanning speech, mild left hearing disturbance, mild to moderate muscle weakness in proximal four extremities, mild bilateral limb ataxia, and mild to moderate truncal ataxia. While, no brisk deep tendon reflex, pathological reflex, aberrant muscle tonus, sensory disturbance, retinopathy, myoclonus or autonomic disorder was found. Serum levels of lactate (23.2 mg/dl, normal<18.7) and pyruvate (1.23 mg/dl, normal<0.94) were elevated, and serum lactate levels were markedly elevated (118.1 mg/dl) after 15-minute exercise (15 Watts/minute). CSF levels of lactate (31.2 mg/dl, normal<12.5) and pyruvate (1.48 mg/dl, normal<0.75) were also elevated. Head MRI showed mild cerebral and cerebellar atrophy, but 1H-MRS showed no lactate peak. Moreover, muscle biopsy from left biceps muscle showed lots of ragged-red fibers, and he was thus diagnosed as having mitochondrial encephalomyopathy. However, nt3243 mutation of mitochondria DNA was not present. Next, we confirmed gynecomastia by mammography, and checked serum levels of estrogens. Mildly decreased estradiol (19.9 pg/ml, normal, 20-59), normal estrone (24.0 pg/ml, normal<30.0) and mildly increased estriol (6.03 pg/ml, normal<5.0) were found. While, the serum levels of cortisol, dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were all within normal limits. Since the steroid hormone synthesis system and hypothalamus-pituitary system seem to be normal, 16alpha-hydroxylase that converts estradiol to estriol may be upregulated. While, aromatase (P-450arom) is well known to convert androgens to estrogens. In addition, 16alpha-hydroxylase and P-450arom convert DHEA-S to estriol. Since it is recently reported that P-450arom is considerably expressed in muscle tissues as well as fat tissues and that muscle tissue may be a major organ to produce estrogens in men and postmenopausal women, estriol production may be increased in the present patient's muscle. Although hypogonadism due to hypothalamus-pituitary disorders was sometimes reported, there have been no reports that suggest an increased estrogen production in skeletal muscles in mitochondrial encephalomyopathies. Recently, estrogen has been known to protect muscle fibers from oxidative damages due to exercise. Thus, it is of potential that estrogens increased locally in muscle tissues of the patients with mitochondrial encephalomyopathies protect muscle fibers from oxidative damage due to mitochondrial dysfunction.
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PMID:[A patient with mitochondrial encephalomyopathy presenting gynecomastia with elevation of serum estriol level]. 1528 12