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)

Lesch-Nyhan disease is a disorder of purine metabolism resulting from mutations in the gene for hypoxanthine guanine phosphoribosyl transferase on the X chromosome. It is characterized by hyperuricemia and all of its consequences, as in gout; but in addition, patients have impressive disease of the central nervous system. This includes spasticity, involuntary movements, and retardation of motor development. The behavioral phenotype is best remembered by self-injurious biting behavior with attendant destruction of tissue. The connection between aberrant metabolism of purines and these neurologic and behavioral features of the disease is not clear. Increasing evidence points to imbalance of neurotransmitters. There is increased excretion of the serotonin metabolite 5-hydroxyindoleacetic acid in the urine. There are decreased quantities and activities of a number of dopaminergic functions. Positron emission tomography scanning has indicated deficiency in the dopamine transporter.
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PMID:Dopamine function in Lesch-Nyhan disease. 1085 37

Primary lateral sclerosis (PLS), the upper motor neurone variant of motor neurone disease, is characterized by progressive spinal or bulbar spasticity with minimal motor weakness. Rarely, PLS may present with clinical features resembling parkinsonism resulting in occasional misdiagnosis as one of the atypical parkinsonian syndromes. Here we describe five patients initially referred with a diagnosis of levodopa-unresponsive atypical parkinsonism (n = 4) or primary progressive multiple sclerosis (n = 1), but subsequently found to have features consistent with PLS instead. Onset age varied from 49 to 67 years. Unilateral limb slowness or clumsiness was the initial complaint in four, and bulbar symptoms in one. Repeated finger/foot tapping was slow in all five, but without fatiguing or decrement. Spasticity with hyperreflexia, exaggerated jaw jerk and extensor plantar responses were eventually seen in all patients. Anterior horn cell involvement developed in three cases. Early gait disturbances resulting in falls were seen in all patients and none of them responded to dopaminergic medications. Two patients underwent dopamine transporter (DaT) SPECT scanning with normal results. Other features included emotional lability (n = 5) and cognitive impairment involving frontal subcortical systems (n = 1). In conclusion, these cases represent a subgroup of PLS patients in whom pyramidal slowness may be mistaken for akinesia, and spasticity misconstrued as rigidity, leading to an erroneous diagnosis of atypical parkinsonism. However, the absence of fatiguing and decrement on repeated finger/foot tapping should help to distinguish these patients from the true atypical parkinsonian syndromes.
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PMID:Primary lateral sclerosis mimicking atypical parkinsonism. 1770 34

Sporadic spastic paraplegia (SSP) and hereditary spastic paraplegia (HSP) belong to a clinical and genetically heterogeneous group of disorders characterized by progressive spasticity and weakness in the lower extremities. The symptoms are associated with pyramidal tract dysfunction and degeneration of the corticospinal tracts. Parkinsonism is uncommon in SSP/HSP patients. However, both disorders are associated with damage to the nigrostriatal dopaminergic system. In the present study, the clinical features of patients with SSP/HSP were investigated, and nigrostriatal dopaminergic binding potential was assessed using dopamine transporter (DAT) single-photon emission computer tomography (SPECT). Nine patients with spastic paraplegia participated in the present study. The subjects underwent DAT SPECT using the agent [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato (3-)-N2,N20,S2,S20]oxo-[IR-(exo-exo)])-[(99)mTc]technetium ([(99)mTc]TRODAT-1). The [(99)mTc]TRODAT-1 SPECT images of five patients appeared normal, whereas the images of four patients revealed reduced striatal ligand uptake. Among the four patients with reduced uptake, two had parkinsonism, and one exhibited periodic limb movements and restless leg syndrome. Our DAT SPECT imaging study shows that reduced DAT density may be observed in patients with parkinsonism. The results of the present study offer an explanation for the spectrum of spastic paraplegia symptoms and the progression of the disorder.
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PMID:Striatal dopaminergic functioning in patients with sporadic and hereditary spastic paraplegias with parkinsonism. 2426 32

We present a series of patients with vertical supranuclear gaze palsy, postural instability with falls, and progressive spasticity, who mimic Progressive Supranuclear Palsy - Richardson's syndrome (PSP-R) but have no parkinsonism, and in whom dopamine transporter imaging is normal. We suggest possible aetiologies for this constellation of symptoms, discuss the possible origin of these signs and highlight this phenotype as it may mimic atypical parkinsonism and in particular PSP.
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PMID:Progressive spasticity, supranuclear gaze palsy and postural instability, without parkinsonism: what's in a phenotype? 2980 13

Variants in the PNPLA6 gene are known to cause 4 distinct phenotypes. One known phenotype is Hereditary Spastic Paraplegia type 39 (HSP 39), a rare neurodegenerative condition characterized by variable onset of lower limb spasticity, weakness and ataxia. Little is known about complications of HSP 39 in adulthood. Here, we report a family of three siblings who presented with bilateral lower limb spasticity in childhood, consistent with HSP, with confirmed bi-allellic PNPLA6 mutations. Two siblings developed parkinsonian features in middle age, a novel finding in this sibship. The proband had a positive dopamine transporter scan, indicating degeneration in dopaminergic neurons, and dopa-responsive extrapyramidal symptoms. Testing for known genetic causes of Parkinsonism was negative. The PNPLA6 gene encodes neuropathy target esterase, an enzyme involved in lipid metabolism that is critical to the stability of cell membranes. We hypothesize that the development of Parkinsonism in these patients may be related to the PNPLA6 mutations, as lipid dysregulation has been implicated in the pathogenesis of Parkinson disease.
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PMID:Bi-allelic variants in PNPLA6 possibly associated with Parkinsonian features in addition to spastic paraplegia phenotype. 3262 94