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

A deficiency of dihydrobiopterin synthesis was found in a 27-year-old man with mild mental retardation, rigid spasticity, hyperreflexia, dystonia, myoclonus, and delay in the initiation of action, since age 10. Symptoms improved after sleep. Urine contained large amounts of neopterin and a trace of biopterin. Dihydropteridine reductase activity in red blood cells was normal. CSF levels of HVA and 5-HIAA were low. Tetrahydrobiopterin administration lowered serum phenylalanine and improved the symptoms.
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PMID:Dihydrobiopterin synthesis defect: an adult with diurnal fluctuation of symptoms. 243 82

Experimental allergic encephalomyelitis (EAE) is widely considered as an animal model of multiple sclerosis (MS). Damage to the bulbospinal serotonergic (5-HT) neurons occurs in the early paralytic stages of EAE in rats with the severity of neurologic signs corresponding to spinal serotonergic depletion. Neurologic recovery of EAE rats is associated with reestablishment of spinal 5-HT transmission possibly through sprouting of undamaged axons and nerve terminals. Damage to the bulbospinal serotonergic fibers also occurs in patients with MS (as reflected by reduced lumbar CSF 5-HIAA levels) and may contribute to several manifestations of the disease including autonomic dysregulation, sensory symptoms (i.e., paresthesias, pain) and motor symptoms (weakness, spasticity, clonus). Spinal serotonergic neuronal sprouting with regeneration of 5-HT nerve terminals may also occur in the early stages of MS and may be associated with spontaneous remission of MS symptoms following an acute relapse. Sprouting of serotonergic neurons may also explain the disparity in MS between the extent of demyelinating plaques and clinical signs of the disease. The chronic course of MS may be associated with progressive axonal degenerative changes with reduction of serotonergic nerve terminals and loss of their sprouting capability. It is proposed that the beneficial effects of treatment with AC pulsed electromagnetic fields on the symptoms and course of the disease in patients with chronic progressive MS may be related in part to renewed sprouting of serotonergic neurons.
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PMID:Serotonergic neuronal sprouting as a potential mechanism of recovery in multiple sclerosis. 1068 Nov 22

Sepiapterin reductase (SR) catalyses the last step in the tetrahydrobiopterin biosynthesis pathway; it converts 6-pyruvoyl-tetrahydropterin (6-PTP) to BH(4) in an NADPH-dependent reaction. SR deficiency is a very rare autosomal recessive disorder with normal phenylalanine (Phe) concentration in blood and diagnostic abnormalities are detected in CSF. We present a 16-month-old girl with SR deficiency. From the newborn period she presented with an adaptation regulatory disorder. At the age of 3 months, abnormal eye movements with dystonic signs and at 4.5 months psychomotor retardation were noticed. Since that time axial hypotonia with limb spasticity (or rather delayed reflex development), gastro-oesophageal reflux and fatigue at the end of the day has been observed. Brain MRI was normal; EEG was without epileptiform discharges. Analysis of biogenic amine metabolites in CSF at the age of 16 months showed very low HVA and 5-HIAA concentrations. Analysis of CSF pterins revealed strongly elevated dihydrobiopterin (BH(2)), slightly elevated neopterin and elevated sepiapterin levels. Plasma and CSF amino acids concentrations were normal. A phenylalanine loading test showed increased Phe after 1 h, 2 h and 4 h and very high Phe/Tyr ratios. SR deficiency was confirmed in fibroblasts and a novel homozygous g.1330C>G (p.N127K) SPR mutation was identified. On L-dopa and then additionally 5-hydroxytryptophan, the girl showed slow but remarkable progress in motor and intellectual ability. Now, at the age of 3 years, she is able to sit; expressive speech is delayed (to 1 1/2 years), passive speech is well developed. Her visual-motor skills, eye-hand coordination and social development correspond to the age of 2 1/2 years.
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PMID:Sepiapterin reductase deficiency in a 2-year-old girl with incomplete response to treatment during short-term follow-up. 1913 Feb 91