1/254. Judicious evaluation of adverse drug reactions: inaccurate assessment of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor-induced muscle injury.Adverse reactions in two patients who received HMG CoA reductase inhibitor therapy were reinvestigated because of their rarity. A case of permanent forearm myalgia was thought to be caused by atorvastatin. Closer evaluation and work-up revealed underlying lateral epicondylitis, and atorvastatin was not considered the cause of the disability. In another patient, rhabdomyolysis was suspected to be secondary to simvastatin. However, after an extensive review, the reaction was believed to be compartment syndrome of the anterior tibial area. An adverse drug reaction report requires careful and judicious assessment to assign the correct probability for the event.- - - - - - - - - - ranking = 1keywords = enzyme (Clic here for more details about this article) |
2/254. The syndrome of carnitine deficiency.Three cases of lipid storage myopathy and carnitine deficiency are presented. Two had a fatal course and were insensitive to cortisone and carnitine-replacement therapy. The two fatal cases had lipid accumulation in organs other than the skeletal muscles and carnitine was reduced in plasma, skeletal muscles, heart and liver. fibroblasts from one of these "generalized" cases of carnitine deficiency were grown from a skin biopsy. Carnitine level, fatty acids uptake and oxidation were not appreciably different between the patients' fibroblasts and those of controls.- - - - - - - - - - ranking = 3.7165191453953keywords = storage (Clic here for more details about this article) |
3/254. An unusual manifestation of diabetes mellitus.MEDICAL history: Type 2 diabetes mellitus for five years; unexplained 35-lb weight loss three years ago; Bell's palsy on right side many years ago. MEDICATIONS: glipizide, 10 mg/day. family history: Father died of leukemia at age 65; mother has kidney stones; no diabetes or neuromuscular disease. SOCIAL history: insurance salesman; heterosexual, promiscuous, uses condoms; smokes (25 pack years); does not drink. physical examination: Well-nourished, well developed, not in acute distress; had difficulty rising from a sitting position because of right lower extremity weakness. blood pressure, 154/74; pulse, 88; temperature, 36.6 degrees C; respiratory rate, 16. head, eyes, ears, nose, and throat: normal. neck: normal. heart: S4. Lungs: clear. abdomen: mildly obese. extremities: no cyanosis, clubbing, or edema; atrophy and weakness of right thigh and both calves; wide-based gait; able to walk on toes but not heels. Neurologic responses: cranial nerves intact; deep tendon reflexes, 1 symmetrically; plantar reflexes, flexor bilaterally. skin: macular rash in sun-exposed areas. LABORATORY FINDINGS: Hemoglobin, 13.2 gm/dL; mean corpuscular volume, 80 micron 3; white blood cell count, 7,200/mm3 (normal differential); platelet count, 137,000/mm3. serum: electrolytes, normal; blood urea nitrogen, 18 mg/dL; creatinine, 0.8 mg/dL; glucose, 308 mg/dL; total protein, albumin, liver enzymes, and creatine kinase, normal. urine: 1 glucose. Venereal disease test: nonreactive; hiv test: negative. DIFFERENTIAL diagnosis: dermatomyositis; heavy-metal poisoning; diabetic amyotrophy. HOSPITAL COURSE: The patient was given 50 mg/day of oral amitriptyline to alleviate the painful paresthesias and was switched to 20 U/day of subcutaneously injected neutral protamine Hagedorn (NPH) insulin to normalize the blood glucose level. Histologic studies of skin and muscle showed sun damage and neuropathic changes, respectively. There was no evidence of vasculitis. Screening for heavy-metal toxins produced negative results.- - - - - - - - - - ranking = 0.25keywords = enzyme (Clic here for more details about this article) |
4/254. exercise intolerance due to a nonsense mutation in the mtDNA ND4 gene.We report the first molecular defect in an NADH-dehydrogenase gene presenting as isolated myopathy. The proband had lifelong exercise intolerance but no weakness. A muscle biopsy showed cytochrome c oxidase (COX)-positive ragged-red fibers (RRFs), and analysis of the mitochondrial enzymes revealed complex I deficiency. sequence analysis of the mitochondrial genes encoding the seven NADH-dehydrogenase subunits showed a G-to-A transition at nucleotide 11832 in the subunit 4 (ND4) gene, which changed an encoded tryptophan to a stop codon. The mutation was heteroplasmic (54%) in muscle dna. Defects in mitochondrially encoded complex I subunits should be added to the differential diagnosis of mitochondrial myopathies.- - - - - - - - - - ranking = 0.25keywords = enzyme (Clic here for more details about this article) |
5/254. Myopathy with trabecular muscle fibers.A systematic review of muscle biopsies over a 15 year period in a large neurological hospital revealed 21 cases (7% of the total of non-inflammatory myopathies) with a distinctive pattern of myopathology and a limb-girdle clinical phenotype. The muscle pathology was dominated by a large prevalence (20-90%) of trabecular or lobulated fibers in which maldistribution of intermyofibrillar mitochondria produced a lobulated pattern of oxidative enzyme activity on transverse sections. The clinical picture was characterized by adult onset, slowly progressive muscle weakness affecting mainly proximal limb musculature, although mild distal weakness was also present in 60% of the cases. The trabecular pattern of oxidative enzyme reaction reflects maldistribution of the intermyofibrillar mitochondria; this may be caused by malfunction of a putative anchoring mechanism. While trabecular fibers can occur as a nonspecific alteration of muscle fibers in many diverse myopathies, the high prevalence of trabecular fibers as the dominant pathology in trabecular fiber myopathy makes it a distinctive (though not necessarily etiologically homogeneous) clinico-pathological entity.- - - - - - - - - - ranking = 0.5keywords = enzyme (Clic here for more details about this article) |
6/254. Myopathy in very-long-chain acyl-coa dehydrogenase deficiency: clinical and biochemical differences with the fatal cardiac phenotype.A 30-year-old man suffered since the age of 13 years from exercise induced episodes of intense generalised muscle pain, weakness and myoglobinuria. fasting ketogenesis was low, while blood glucose remained normal. Muscle mitochondria failed to oxidise palmitoylcarnitine. Palmitoyl-CoA dehydrogenase was deficient in muscle and fibroblasts, consistent with deficiency of very-long-chain acyl-coa dehydrogenase (VLCAD). The gene of this enzyme had a homozygous deletion of three base pairs in exon 9, skipping lysine residue 238. fibroblasts oxidised myristate, palmitate and oleate at a rate of 129, 62 and 38% of controls. In contrast to patients with cardiac VLCAD deficiency, our patient had no lipid storage, a normal heart function, a higher rate of oleate oxidation in fibroblasts and normal free carnitine in plasma and fibroblasts. 31P-nuclear magnetic resonance spectroscopy of muscle showed a normal oxidative phosphorylation as assessed by phosphocreatine recovery, but a significant increase in pH and in Pi/ATP ratio.- - - - - - - - - - ranking = 3.9665191453953keywords = storage, enzyme (Clic here for more details about this article) |
7/254. Infantile lipid storage myopathy with nocturnal hypoventilation shows abnormal low-affinity muscle carnitine uptake in vitro.An infant with respiratory insufficiency, cardiomyopathy, lipid storage myopathy and low muscle carnitine was diagnosed as having 'Ondine's curse' because of recurrent nocturnal hypoventilation. Carnitine uptake was studied in 20-day-old cultured muscle, where two distinct saturable transport components are recognized: the high- and low-affinity-uptake. Experimental evidence suggests that low-affinity-uptake is muscle-specific, operating at physiological carnitine concentration. In the patient's cultured myotubes, the low-affinity-uptake K(m) was 260% of controls (P < 0.01), whereas kinetic parameters of high-affinity uptake were normal. The high K(m) indicates an immature or altered carnitine muscle carrier, which may decrease the physiologic carnitine uptake.- - - - - - - - - - ranking = 18.582595726976keywords = storage (Clic here for more details about this article) |
8/254. Early-onset fetal hydrops and muscle degeneration in siblings due to a novel variant of type IV glycogenosis.We report on 3 consecutive sib fetuses, presenting at 13, 12, and 13 weeks of gestation, respectively, with fetal hydrops, limb contractures, and akinesia. autopsy of the first fetus showed subcutaneous fluid collections and severe degeneration of skeletal muscle. Histologic studies demonstrated massive accumulation of diastase-resistant periodic acid-Schiff-positive material in the skeletal muscle cells and epidermal keratinocytes of all 3 fetuses. Enzyme studies of fibroblasts from the 3rd fetus showed deficient activity of glycogen brancher enzyme, indicating that this is a new, severe form of glycogenosis type IV with onset in the early second trimester.- - - - - - - - - - ranking = 0.25keywords = enzyme (Clic here for more details about this article) |
9/254. Noninvasive evaluation of adult onset myopathy from carnitine palmitoyl transferase II deficiency using proton magnetic resonance spectroscopy.OBJECTIVE: The adult onset metabolic myopathy of carnitine palmitoyl transferase II (CPT II) deficiency is under-recognized, in part due to variable degrees of enzyme deficiency and symptomatology, as well as limitations in means for noninvasive evaluation. We describe a proton magnetic resonance spectroscopy (MRS) technique, using a standard clinical magnetic resonance imaging scanner, to diagnose and help monitor the response to therapy in adult CPT II deficiency. methods: A 53-year-old woman presented with a long standing history of diffuse aching and fatigue provoked by high fat intake, fasting, or prolonged exertion. Muscle biopsy revealed myopathic features and a deficiency (33% of control) of CPT II activity with elevated palmitoyl carnitine. Proton MRS of the soleus muscle was performed using a 1.5 Tesla scanner before and during dietary therapy. RESULTS: Proton MRS revealed shortening of the transverse relaxation time (T2), consistent with increased acetylation of the carnitine pool. The symptoms resolved completely by treatment with frequent feedings of a high carbohydrate diet low in long chain fatty acids supplemented with medium chain triglycerides and L-carnitine. Recovery of normal muscle MRS and carnitine T2 relaxation was documented by the third month of therapy. CONCLUSION: Proton MRS is a novel, potentially useful, and readily available adjunct in the diagnosis and therapeutic monitoring of muscle CPT II deficiency.- - - - - - - - - - ranking = 0.25keywords = enzyme (Clic here for more details about this article) |
10/254. A novel missense mutation in the glycogen branching enzyme gene in a child with myopathy and hepatopathy.We have identified a novel missense mutation in the gene for glycogen branching enzyme (GBE 1) in a 16-month-old infant with a combination of hepatic and muscular features, an atypical clinical presentation of glycogenosis type IV (GSD IV). The patient was heterozygous for a G-to-A substitution at codon 524 (R524Q), changing an encoded arginine (CGA) to glutamine (CAA), while the GBE1 gene on the other allele was not expressed. This case broadens the spectrum of mutations in patients with GSD IV and confirms the clinical and molecular heterogeneity of this disease.- - - - - - - - - - ranking = 1.25keywords = enzyme (Clic here for more details about this article) |
| | Next -> |