Biotin-related abnormalities in human metabolism

Recent work has led to the discovery that two severe hereditary human pathologies are caused by biotin deficiency. Significantly, administration of pharmacologic doses of biotin can provide clinically effective treatment. Both diseases are autosomal recessive in inheritance but differ in their associated enzymatic deficiencies. The clinical, enzymatic, and genetic characteristics of these pathologies are reviewed here.     

Tiglicaciduria in propionicacidaemia

Tiglic acid, which has not previously been found in human body fluids, was recently detected in the urine of two patients with propionicacidaemia. These patients had a documented defect in the oxidation of propionate. A competition between acrylyl-CoA and tiglyl-CoA for crotonase could explain the accumulation of tiglic acid.     

Abnormal metabolites of isoleucine in a patient with propionyl-CoA carboxylase deficiency

A number of previously unrecognized abnormal metabolites have been identified and quantitated in the urine of a patient with an inherited deficiency of propionyl-CoA carboxylase. These included the isoleucine metabolites 2-methyl-3-hydroxybutyric acid and 2-methylacetoacetic acid. These isomers 3-hydroxyvaleric acid and 3-oxovaleric acid were found, which may be products of the condensation of propionyl-CoA with acetyl-CoA catalyzed by 3-oxoacyl-CoA thiolases. Following a load of isoleucine, 2-methylbutyrylglycine was identified. This metabolite has not previously been observed in man.     

Wavelet-based Gaussian-mixture hidden Markov model for the detection of multistage seizure dynamics: A proof-of-concept study

Background  

Epilepsy is a common neurological disorder characterized by recurrent electrophysiological activities, known as seizures. Without the appropriate detection strategies, these seizure episodes can dramatically affect the quality of life for those afflicted. The rationale of this study is to develop an unsupervised algorithm for the detection of seizure states so that it may be implemented along with potential intervention strategies.     

Lesch-Nyhan disease

Lesch-Nyhan disease is the most severe or complete phenotype of deficiency in hypoxanthineguanine phosphoribosyltransferase; other variant enzymes are found in patients without abnormality in behavior or mental development, and there are intermediate phenotypes in which enzyme activity is intermediate. A considerable number and variety of mutations in the HPRT gene have been discovered.