Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two families of dogs (Australian cattle dogs and Shetland sheepdogs) with an inherited "spongiform leukoencephalomyelopathy" were identified, with widespread vacuolation of white matter of the brain and spinal cord. Affected dogs of both breeds developed tremors at 2-9 weeks of age followed by progressive neurological worsening with ataxia, paresis, paralysis, spasticity, and cranial nerve dysfunction. The modes of inheritance of both families were most likely maternal. The cerebrospinal fluid (CSF) analysis showed elevated ratio of 3-OH butyrate to acetoacetic acid. Mitochondrial DNA sequencing showed a G to A transition at 14,474 nt (G14474A, GenBank accession no. NC002008 ) that results in an amino acid change of valine-98 to methionine (V98M) of mitochondrial encoded cytochrome b. Western blot analysis showed increased levels of core I and core II but decreased level of cytochrome c1 of the complex III and cytochrome c oxidase of the complex IV of the respiratory chain.
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PMID:Canine spongiform leukoencephalomyelopathy is associated with a missense mutation in cytochrome b. 1602 96

Mitochondrial myopathies make up a group of rare disorders whose onset is in childhood or adolescence. Muscle and central nervous system involvement is variable. Mitochondrial respiratory chain complex III deficiency (coenzyme Q - cytochrome C reductase) can manifest as exercise intolerance, myopathy, encephalopathy, and myocardial disease. Approximately 38 patients with complex III deficiency have been described since 1966, yet only a single anesthetic experience (epidural analgesia for cesarean delivery) has been reported. We describe the case of an 11-year-old boy with mitochondrial respiratory chain complex III deficiency, severe myopathy, and moderate encephalopathy who underwent surgery to improve right ischiotibial muscle spasticity. Monitoring included electrocardiography, noninvasive blood pressure, oxygen saturation by pulse oximetry, end-tidal carbon dioxide pressure, esophageal temperature, spirometry, and neuromuscular block (Relaxograph Datex). Midazolam, fentanyl, and propofol were used for anesthetic induction; mivacurium was used during intubation. Anesthetic maintenance was with propofol in continuous infusion and fractionated doses of fentanyl and mivacurium on demand in a mixture of oxygen and air. The boy's response to mivacurium was abnormal but he could nevertheless be extubated in the operating room at a train-of-four ratio of 75% and with no need to reverse the neuromuscular blockade. There were no problems during the anesthetic procedure, so it could be a good technique for these patients, despite of considering individually every case and extension of syntomatology, due to the little experience in anesthesia with deficiency of Complex III.
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PMID:[Anesthesia for a patient with mitochondrial respiratory chain complex III deficiency]. 1729 35

Hereditary spastic paraplegias (HSPs) are a diverse class of neurodegenerative disorders that mainly affect the corticospinal tract of the body and result in various clinical conditions such as lower limb spasticity and muscle weakness in the lower extremities. Worldwide, more than 70 chromosomal loci/genes have been reported to be associated with HSPs, out of which, six genes viz., ATL1, FA2H, GJC2, AP4E1, ALDH18A1 and ATP13A2 have been mapped in Pakistani families. In the present genetic study, we report on a large consanguineous Pakistani family with a complex form of HSP segregating with a 18 bp deletion in the first exon of the Fatty Acid 2-Hydroxylase (FA2H) gene (NM_024306.5:c.159_176del). The identified in-frame deletion results in loss of six amino acids (p.Arg53_Ile58del) within the cytochrome B5 domain of the protein. FA2H is required for alpha-hydroxylation of free fatty acids to form alpha-hydroxylated sphingolipids. Its cytochrome b5-like heme-binding domain, which spans from residues 15 to 85, imparts the redox activity to FA2H. This mutation has previously been reported in a Pakistani family presenting with a similar form of complex HSP. Together with our findings the pathogenic role of the observed variant is further supported. Mutation studies on additional Pakistani families for FA2H will further elucidate its mutational spectrum, which may help in developing a prenatal diagnostic test for Khyber Pakhtunkhwa resident Pakistani families.
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PMID:Exome sequencing of a Pakistani family with spastic paraplegia identified an 18 bp deletion in the cytochrome B5 domain of FA2H. 3324 95