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)

Succinic semialdehyde dehydrogenase deficiency is one of the disorders of GABA metabolism, so it is not surprising that seizures occur as one of the symptoms in affected patients. Other features that are described include delayed development, hypotonia, myopathy with ragged red fibres, abnormal behaviour, and ocular abnormalities. Neonatal problems include prematurity, respiratory difficulties, and hypoglycaemia. The responsible gene has been identified on the short arm of chromosome 6. There are many mutations, and there is poor genotype-phenotype correlation resulting in difficulties in diagnosis. The pathogenesis of the condition is discussed, especially the results of the disturbed GABA catabolism, and the production of the gamma-hydroxybutyric acid. The many properties of this substance suggest it may act as a neurotransmitter or neuromodulator in the brain. The diagnosis may be difficult as the clinical picture is not really suggestive, but the MRI examination can help if it shows abnormalities in the globus pallidus. It will be confirmed by finding an excess of 4-hydroxybutyric acid in the body fluids; and the methods of estimation are discussed. Prenatal diagnosis is possible using a combination of methods. Treatment possibilities are limited. Vigabatrin should be of value as it is an inhibitor of GABA transaminase, but results have been disappointing. Symptomatic treatment may well be needed for control of seizures, abnormal behaviour and other disorders; and special educational needs must be served.
 ...
PMID:Succinic semialdehyde dehydrogenase deficiency (SSADH) (4-hydroxybutyric aciduria, gamma-hydroxybutyric aciduria). 1534 10

West syndrome (WS) is an age dependent epileptic syndrome caused by various brain disorders. WS has been frequently classified in two groups, cryptogenic and symptomatic. As symptomatic WS consists of patients with numerous types of brain lesions, the prognosis and evolutional changes may be different among the types of brain lesions. WS is resistant to treatment to most conventional antiepileptic drugs, and only valproic acid, benzodiazepines, adrenocorticotropic hormone (ACTH), corticosteroids and vigabatrin have been found efficacious. Benzodiazepine, notably nitrazepam, and less clonazepam had been effective in bringing spasms under control but emerging tolerance and significant side effects (hypotonia and drowsiness) precluded its wider use. ACTH has been the treatment of choice for infantile spasms ever since Sorel and Dusaucy-Bouloye described its effectiveness in 1958. Despite the empirical approach steroids were capable of controlling the spasms and normalizing EEG in about 60% of cases. Corticotropin (ACTH) was used in doses from 5 to 180 I.U. daily, prednizolone 2-10 mg/kg daily, hydrocortisone 5-10 mg/kg daily and dexamethason 0.3-0.5 mg/kg. However, poor consensus was defined regarding the best steroid molecule to use, the dosage, and the duration of treatment. Also frequent and sometimes serious side effects have occurred during ACTH therapy, notably serious infections and hypertension that promoted continuous search for alternative and safer drugs tolerated outpatient treatment, good tolerance and minor side effects. Recently a specific visual field loss has been reported in treated adults that raised concern about safety of vigabatrin. New reports in children claim that vigabatrin treatment of children and adolescents has a lower risk for visual field defect than in adults, because of reported reversibility. Vigabatrin paediatric advisory group recommend the trial of vigabatrin for 12-14 days as first treatment for WS and in the case of good clinical response continuation of therapy for six months. Other new antiepileptic drugs (lamotrigine, topiramate, felbamate and zonisamide) have shown significant efficacy in the treatment of resistant WS to previous medication. The current task is to determine risk/benefit ratios of these two drugs (vigabatine, ACTH) and to delineate the group of patients with WS where their use would be optimal.
 ...
PMID:[West syndrome--new therapeutic approach]. 1563 97