Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The actions of the serotonin precursor 5-hydroxytryptophan (5-HTP), the agonist 5-methoxy-N,N-dimetyltryptamine (MeODMT) and quipazine (QPZ) and the antagonists cyproheptadine, methysergide and metergoline, were studied in the rat and in the common marmoset (Callithrix jacchus). The precursor and agonists elicited head shakes, forepaw padding, splayed hindlimbs, tremor and Straub tail in the rat. However, head shakes were not observed after MeODMT and Straub tail was not observed after QPZ. Carbidopa plus 5-HTP potentiated only head shakes, while tranylcypromine (TCP) plus 5-HTP potentiated all the behaviors above. In the marmoset, the action of these drugs elicited drowsiness, teeth chattering, ataxia, vomiting and decreased motor activity, although vomiting was not elicited by MeODMT and ataxia and drowsiness by QPZ. Although TCP plus 5-HTP potentiated all these behaviors, carbidopa plus 5-HTP was not effective. Rats treated with the antagonists (1.0, 5.0 and 10 mg/kg doses) did not show any of these behaviors, but marmosets treated with the same drugs developed "drowsiness", vomiting, and decreased motor activity; nonetheless, cyproheptadine (5.0 and 10 mg/kg doses) did not elicit "drowsiness", while increasing motor activity and the number of head shakes. Pretreatment of marmosets with these antagonists blocked only teeth chattering elicited by MeODMT (4.0 mg/kg) and QPZ (10 mg/kg). Pretreatment with haloperidol, p-chlorophenylalanine and alpha-methyl-P-tyrosine had no effect. The data obtained show that rats and marmosets present differential behavioral responses to the 5-HT drugs used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rats and marmosets respond differently to serotonin agonists and antagonists. 311 2

Clinical picture of neuronal ceroid lipofuscinosis with late infantile onset (LINCL) is characterized by myoclonic seizures and psychomotor regression. We present a case of classic LINCL and reduced cerebrospinal fluid (CSF) pterins in a girl of normal psychomotor development and born to non-consanguineous parents. She first presented with febrile seizures at the age of four. At that time, brain computed tomography finding was normal, but electroencephalogram showed hypsarrhythmia. At the age of five, tremor, generalized ataxia, and motor and mental regression appeared. Brain magnetic resonance imaging showed cerebellar atrophy. Electron microscopy examination showed storage of intracytoplasmic curvilinear inclusions in neurons, fibroblasts, and secretory cells of the skin and rectal mucosa. Tripeptidyl peptidase I (TPP-I) activity in leukocytes was very low (5.4 nmol/h/mg protein; range in homozygote cases of LINCL, 0.4-26.0). Molecular genetic studies showed a homozygous mutation, R208X, in exon 6 of CLN2 gene. CSF analysis revealed very low neopterin (7.3 nmol/L; normal range, 9-30) and biopterin (4.1 nmol/L; normal range, 10-30), reduced homovanillic acid (266 nmol/L; normal range, 211-871), and low homovanillic acid/5-hydroxyindoleacetic acid ratio (1.21; normal ratio, 1.5-3.5). Treatment with L-Dopa/Carbidopa (4 mg/kg) and antiepileptics was introduced, but without significant effect. It seems that low CSF pterins and impaired dopamine turnover are secondary manifestations of classical LINCL caused by homozygous inheritance of the R208X mutation in CLN2 gene.
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PMID:R208X mutation in CLN2 gene associated with reduced cerebrospinal fluid pterins in a girl with classic late infantile neuronal ceroid lipofuscinosis. 1295 Jan 56

We describe neurotransmitter abnormalities in two patients with drug-resistant epilepsy resulting from deleterious de novo mutations in sodium channel genes. Whole exome sequencing identified a de novo SCN2A splice-site mutation (c.2379+1G>A, p.Glu717Gly.fs*30) resulting in deletion of exon 14, in a 10-year old male with early onset global developmental delay, intermittent ataxia, autism, hypotonia, epileptic encephalopathy and cerebral/cerebellar atrophy. In the cerebrospinal fluid both homovanillic acid and 5-hydroxyindoleacetic acid were significantly decreased; extensive biochemical and genetic investigations ruled out primary neurotransmitter deficiencies and other known inborn errors of metabolism. In an 8-year old female with an early onset intractable epileptic encephalopathy, developmental regression, and progressive cerebellar atrophy, a previously unreported de novo missense mutation was identified in SCN8A (c.5615G>A; p.Arg1872Gln), affecting a highly conserved residue located in the C-terminal of the Nav1.6 protein. Aside from decreased homovanillic acid and 5-hydroxyindoleacetic acid, 5-methyltetrahydrofolate was also found to be low. We hypothesize that these channelopathies cause abnormal synaptic mono-amine metabolite secretion/uptake via impaired vesicular release and imbalance in electrochemical ion gradients, which in turn aggravate the seizures. Treatment with oral 5-hydroxytryptophan, l-Dopa/Carbidopa, and a dopa agonist resulted in mild improvement of seizure control in the male case, most likely via dopamine and serotonin receptor activated signal transduction and modulation of glutamatergic, GABA-ergic and glycinergic neurotransmission. Neurotransmitter analysis in other sodium channelopathy patients will help validate our findings, potentially yielding novel treatment opportunities.
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PMID:Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target? 2918 79