This is a report of the findings of a 6-year study of hospitalizations caused by adverse psychiatric reactions to prescribed medications. Of 15,800 consecutive psychiatric admissions to two university hospitals, 112 (0.7%) were caused by adverse reactions to medications. In 67% of cases these admissions were due to extrapyramidal symptoms such as parkinsonism and/or akathisia, and coexisting neuroleptic-related depression. In 25% the admitting diagnosis was drug-induced delirium or psychosis; one third of these patients suffered from Parkinson's disease and had been treated with a combination of two or more antiparkinsonian agents. Older age, polydrug therapy, and the parenteral administration of neuroleptics at high dosages were important risk factors for severe adverse drug reactions leading to hospitalization.

Adult↗

PubMedDate not supplied

Seventeen novel mutations that cause profound biotinidase deficiency.

We report 17 novel mutations that cause profound biotinidase deficiency. Six of the mutations are due to deletions, whereas the remaining 11 mutations are missense mutations located throughout the gene and encode amino acids that are conserved in mammals. Our results increase the total number of different mutations that cause biotinidase deficiency to 79. These additional mutations will undoubtedly be helpful in identifying structure/function relationships once the three-dimensional structure of biotinidase is determined.

Amidohydrolases↗

PubMedDate not supplied

Fine mapping of the human biotinidase gene and haplotype analysis of five common mutations.

Biotinidase deficiency is an autosomal recessive defect in the recycling of biotin that can lead to a variety of neurologic and cutaneous symptoms. The disease can be prevented or effectively treated with exogenous biotin. The biotinidase locus (BTD) has been maped to 3p25 by in situ hybridization. The gene has been cloned, the coding region sequenced, the genomic organization determined, and a spectrum of mutations has been characterized in more than 90 individuals with profound or partial biotinidase deficiency. We have conducted haplotype analysis of 10 consanguineous and 39 nonconsanguineous probands from the United States and 8 consanguineous probands from Turkey to localize BTD with respect to polymorphic markers on 3p and to investigate the origins of five common mutations. The inbred probands were homozygous for overlapping regions of 3p ranging in size from 1.1 to 80 cM which were flanked most narrowly by D3S1259 and D3S1293. Radiation hybrids and haplotype analysis of markers within this region suggest that BTD is located within a 0.1-cM region flanked by D3S3510 and D3S1286. The radiation hybrid data suggest that the BTD gene is oriented 5' to 3' between the centromere and the 3p telomere. Association studies indicate that the gene is closer to a third locus D3S3613 than D3S3510, two markers which cannot be resolved by existing linkage data. The BTD locus and D3S3613 must therefore lie between D3S3510 and D3S1286. Comparison of haplotypes reveals evidence for possible founder effects for four of the five common mutations.

Adult↗