Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tetrahydrobiopterin (BH4) is synthesized from guanosine triphosphate (GTP) by GTP cyclohydrolase I (GCH), 6-pyruvoyltetrahydropterin synthase (PTS), and sepiapterin reductase (SPD). GCH is the rate-limiting enzyme. BH4 is a cofactor for three pteridine-requiring monooxygenases that hydroxylate aromatic L-amino acids, i.e., tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and phenylalanine hydroxylase (PAH), as well as for nitric oxide synthase (NOS). The intracellular concentrations of BH4, which are mainly determined by GCH activity, may regulate the activity of TH (an enzyme-synthesizing catecholamines from tyrosine), TPH (an enzyme-synthesizing serotonin and melatonin from tryptophan), PAH (an enzyme required for complete degradation of phenylalanine to tyrosine, finally to CO2 + H2O), and also the activity of NOS (an enzyme forming NO from arginine), Dominantly inherited hereditary progressive dystonia (HPD), also termed DOPA-responsive dystonia (DRD) or Segawa's disease, is a dopamine deficiency in the nigrostriatal dopamine neurons, and is caused by mutations of one allele of the GCH gene. GCH activity and BH4 concentrations in HPD/DRD are estimated to be 2-20% of the normal value. By contrast, recessively inherited GCH deficiency is caused by mutations of both alleles of the GCH gene, and the GCH activity and BH4 concentrations are undetectable. The phenotypes of recessive GCH deficiency are severe and complex, such as hyperphenylalaninemia, muscle hypotonia, epilepsy, and fever episode, and may be caused by deficiencies of various neurotransmitters, including dopamine, norepinephrine, serotonin, and NO. The biosynthesis of dopamine, norepinephrine, epinephrine, serotonin, melatonin, and probably NO by individual pteridine-requiring enzymes may be differentially regulated by the intracellular concentration of BH4, which is mainly determined by GCH activity. Dopamine biosynthesis in different groups of dopamine neurons may be differentially regulated by TH activity, depending on intracellular BH4 concentrations and GCH activity. The nigrostriatal dopamine neurons may be most susceptible to a partial decrease in BH4, causing dopamine deficiency in the striatum and the HPD/DRD phenotype.
 ...
PMID:Regulation of pteridine-requiring enzymes by the cofactor tetrahydrobiopterin. 1032 73

The clinical data and the imaging findings of the positron emission tomography (PET) and the magnetic resonance imaging (MRI) studies in five patients, previously diagnosed to have propionic acidemia, were retrospectively reviewed. The patients were all normal at birth. The first clinical signs, typically hypotonia and failure to thrive, appeared during the first 2 years of life. With progression of the disease, the neurological findings consisted of variable degrees of dementia and extrapyramidal symptoms, notably dystonia, choreoathetosis and rigidity of variable degrees. Initial cerebral PET and MRI studies were normal. Follow-up MRI examinations showed progressive basal ganglia degeneration, with evidence of atrophy and signal abnormalities within the caudate nuclei and the putamina. The thalamic structures were normal. The PET studies demonstrated increased uptake in the basal ganglia and thalami, followed by decreased uptake in the basal ganglia at a later stage of the disease. The structural (MRI) and the functional (PET) studies of the brain were found to be complementary in the evaluation of propionic acidemia, and were in good correlation with the clinical findings.
 ...
PMID:18Fluoro-2-deoxyglucose (18FDG) PET scan of the brain in propionic acidemia: clinical and MRI correlations. 1041 18

The clinical phenotype and the molecular defect of a patient with a new subtype of congenital disorders of glycosylation (CDG-Ic, formerly designated as CDGS type V) characterized by a deficiency of Dol-P-Glc: Man9GlcNAc2-PP-Dol glucosyltransferase is described. The clinical picture presents with several features similar to CDG-Ia (phosphomannomutase 2 deficiency) such as hypotonia and atactic-dystonic movements. In contrast to CDG-Ia, the course of the disease appears milder. The head growth, the functioning of the peripheral nerves and the initial cerebellar development were normal. Sequencing of the patient's Dol-P-Glc: Man9GlcNAc2-PP-Dol glucosyltransferase cDNA revealed an in-frame deletion of three nucleotides leading to the loss of isoleucine 299.
 ...
PMID:Congenital disorder of glycosylation-Ic: case report and genetic defect. 1083 77

Dopa-responsive dystonia (DRD) is an autosomal dominant disorder typically presenting as dystonia with diurnal variability. Described is an 8-year-old boy who had had waddling gait, generalized hypotonia, and proximal weakness since early childhood. He responded well to low-dose L-dopa. He had a point mutation of the GTP cyclohydrolase I gene. The patient's father and sister had the same mutation but did not have proximal weakness. GTP cyclohydrolase I deficiency can present with hypotonia and weakness.
 ...
PMID:Atypical presentation of dopa-responsive dystonia: generalized hypotonia and proximal weakness. 1157 50

Glutaric aciduria typo I (GA I) is an uncommon metabolic disease with autosomal recessive inheritance. It usually presents in the first years of life and frequently causes movement disorders. Only a few cases have been diagnosed in adulthood. Two siblings who were diagnosed of GA I after a course of more than 20 years are reported here. The elder brother, after 9 months of normal psychomotor development, suffered from an acute encephalopathy with generalized hypotonia and, later on, dyskinetic movements. Throughout the following years severe generalized dystonia developed. The younger brother presented at 16 months with acute encephalopathy, hypotonia and generalized choreoathetoid movements. Cranial computed tomography showed in both patients an slight enlargement of Silvian cisures and diffuse white matter hypodensities. Magnetic resonance imaging performed in the second case disclosed in addition bilateral hyperintensities in putamen and caudate nucleous. At 29 and 24 years of age, respectively, an increased urinary excretion of glutaric and 3-hydroxiglutaric acids was detected in both patients. Glutaryl-CoA deshidrogenase activity in fibroblasts was absent in both. The patients were treated with carnitine and riboflavine, with no response. The present report shows that diagnosis of GA I should be considered in adults presenting a range of movement disorders from childhood.
 ...
PMID:[Glutaric aciduria type I: diagnosis in adulthood and phenotypic variability]. 1173 16

Inherited metabolic disorders can cause onset of epilepsy in the first year of life. Epilepsy rarely dominates the clinical presentation, which is more frequently associated with other neurologic symptoms, such as mental retardation, hypotonia and/or dystonia, or vigilance disturbances. The pathogenesis of seizures is multifaceted; inherited metabolic disorder can affect the balance between excitatory and inhibitory chemical mediators, eliminate an energetic substrate at the cerebral level, cause in utero brain malformation, or provoke acute brain lesions. Some clinical disorders that strongly suggest particular metabolic etiologies can be identified. For example, specific clinical signs and findings on electroencephalogram (EEG) are characteristic of pyridoxine-dependent seizures, and inherited metabolic disorders associated with early myoclonic encephalopathy are well defined. In most cases, however, epilepsy secondary to inherited metabolic disorders presents with polymorphic clinical and EEG features that are difficult to classify into precise epileptic syndromes. Common characteristics of these seizures include onset in the first months of life; usually partial, multifocal; simple partial motor semiology; successive appearance of tonic seizures, spasms, and massive myoclonus; and resistance to antiepilepsy drugs. Inherited metabolic disorders must be considered in patients presenting with epilepsy and progressive neurologic worsening.
 ...
PMID:Infantile epileptic syndromes and metabolic etiologies. 1259 51

Mutations in the MECP2 (methyl-CpG-binding protein 2) gene are known to cause Rett syndrome, a well-known and clinically defined neurodevelopmental disorder. Rett syndrome occurs almost exclusively in females and for a long time was thought to be an X-linked dominant condition lethal in hemizygous males. Since the discovery of the MECP2 gene as the cause of Rett syndrome in 1999, MECP2 mutations have, however, also been reported in males. These males phenotypically have classical Rett syndrome when the mutation arises as somatic mosaicism or when they have an extra X chromosome. In all other cases, males with MECP2 mutations show diverse phenotypes different from classical Rett syndrome. The spectrum ranges from severe congenital encephalopathy, mental retardation with various neurological symptoms, occasionally in association with psychiatric illness, to mild mental retardation only. We present a 21-year-old male with severe mental retardation, spastic tetraplegia, dystonia, apraxia and neurogenic scoliosis. A history of early hypotonia evolving into severe spasticity, slowing of head growth, breathing irregularities and good visual interactive behaviour were highly suggestive of Rett syndrome. He has a de novo missense mutation in exon 3 of the MECP2 gene (P225L). The clinical spectrum and molecular findings in males with MECP2 mutations are reviewed.
 ...
PMID:Neurodevelopmental disorders in males related to the gene causing Rett syndrome in females (MECP2). 1261 69

Selected spastic patients with cerebral palsy can be helped by peripheral reconstructive surgery, of the upper limb. Although surgery cannot make a limb that was functionally poor into a perfect one, it can greatly improve the preoperative condition. Most poor surgical results are caused by incorrect selection of patients or poor execution of surgical procedures. The worst mistake is to perform soft tissue procedures--tendinous release or tendinous transfers--on a patient with pure athetosis. The results in these cases are unpredictable and often fail. The same concept is applied to rigidity, hypotonia, dystonia, and ataxia. The surgical program is organized according to the type and severity of the deformity (clinical groups). The goals are to correct the deformities and to improve the muscular balance of the hand in one surgical stage. It must be remembered that spastic muscle cannot be used for tendon transfer with the same efficiency as in patients with a flaccid paralysis. Results were satisfactory in 92% of cases of groups I and II. If group III is included, the percentage of satisfactory results reduces significantly.
 ...
PMID:Surgical management of the hand in infantile spastic hemiplegia. 1459 53

Thyroid hormones are iodothyronines that control growth and development, as well as brain function and metabolism. Although thyroid hormone deficiency can be caused by defects of hormone synthesis and action, it has not been linked to a defect in cellular hormone transport. In fact, the physiological role of the several classes of membrane transporters remains unknown. We now report, for the first time, mutations in the monocarboxylate transporter 8 (MCT8) gene, located on the X chromosome, that encodes a 613-amino acid protein with 12 predicted transmembrane domains. The propositi of two unrelated families are males with abnormal relative concentrations of three circulating iodothyronines, as well as neurological abnormalities, including global developmental delay, central hypotonia, spastic quadriplegia, dystonic movements, rotary nystagmus, and impaired gaze and hearing. Heterozygous females had a milder thyroid phenotype and no neurological defects. These findings establish the physiological importance of MCT8 as a thyroid hormone transporter.
 ...
PMID:A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. 1466 Nov 63

Reports describing the neurological features of Lesch-Nyhan disease (LND) vary widely, thereby implying the involvement of different neurological substrates. The movement abnormalities in 20 patients with LND were investigated. Dystonia was the most frequent and severe movement disorder. At rest, hypotonia was more frequent than hypertonia. These findings are compatible with basal ganglia dysfunction in LND.
 ...
PMID:The motor disorder of classic Lesch-Nyhan disease. 1557 Dec 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>