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Biomedical subjects

Stephen Cederbaum

Publications and source records attributed to Stephen Cederbaum.

5 recordsLinked to original sources
PubMed2006

Expanded newborn screening identifies maternal primary carnitine deficiency.

Primary carnitine deficiency impairs fatty acid oxidation and can result in hypoglycemia, hepatic encephalopathy, cardiomyopathy and sudden death. We diagnosed primary carnitine deficiency in six unrelated women whose unaffected infants were identified with low free carnitine levels (C0) by newborn screening using tandem mass spectrometry. Given the lifetime risk of morbidity or sudden death, identification of adult patients with primary carnitine deficiency is an added benefit of expanded newborn screening programs.

Adult↗
PubMed2002

Organization of the human liver carnitine palmitoyltransferase 1 gene ( CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia.

Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare autosomal recessive disorder of mitochondrial fatty acid oxidation. CPT1 controls the import of long-chain fatty acids into the mitochondria, where they are oxidized. Two CPT1 isoforms, the so-called "liver" and "muscle" CPT1s encoded by the CPT1Aand CPT1Bgenes, respectively, have been identified so far. While the cDNA sequences of both isoforms are known, only CPT1Bgene organization has yet been described. We took advantage of the working draft data to characterize the organization of the human CPT1A gene. We have shown the existence of 20 exons, spanning 60 kb of DNA. Two alternate promoters and numerous transcription factor-binding sites were identified within the 5' upstream region of the gene. In the 3' untranslated region, the major polyA signal was suggested to lie about 2 kb downstream of the stop codon. These data enabled us to characterize six novel mutations in four CPT1A-deficient patients; namely Q100X (exon 4), A414 V (exon 11), Y498C (exon 13), 1876-1G>A (intron 15), a 113-bp intronic insertion in the mature CPT1A mRNA (exon 13-14 junction), and a large 8-kb deletion encompassing intron 14 to exon 17. Thus, identification of the CPT1A gene organization contributes to improve the molecular screening in patients and provides tools for the study of the human CPT1A gene expression.

Blotting, Northern↗
PubMed2002

Phenylketonuria: an update.

Phenylketonuria is a flagship inborn error of metabolism and has been at the forefront of our growing understanding, diagnosis, and treatment of this family of disorders. In this article, the current understanding of its diagnosis, treatment, and complex molecular biology and physiology is reviewed. Recent papers exploring newer and less well-delineated areas of cofactor supplementation and genetic and epigenetic modification of the genotypic expression are presented. The excitement surrounding the continued exploration of the hyperphenylalaninemias is emphasized.

Animals↗
PubMed2002

Biotin dependency due to a defect in biotin transport.

We describe a 3-year-old boy with biotin dependency not caused by biotinidase, holocarboxylase synthetase, or nutritional biotin deficiency. We sought to define the mechanism of his biotin dependency. The child became acutely encephalopathic at age 18 months. Urinary organic acids indicated deficiency of several biotin-dependent carboxylases. Symptoms improved rapidly following biotin supplementation. Serum biotinidase activity and Biotinidase gene sequence were normal. Activities of biotin-dependent carboxylases in PBMCs and cultured skin fibroblasts were normal, excluding biotin holocarboxylase synthetase deficiency. Despite extracellular biotin sufficiency, biotin withdrawal caused recurrent abnormal organic aciduria, indicating intracellular biotin deficiency. Biotin uptake rates into fresh PBMCs from the child and into his PBMCs transformed with Epstein Barr virus were about 10% of normal fresh and transformed control cells, respectively. For fresh and transformed PBMCs from his parents, biotin uptake rates were consistent with heterozygosity for an autosomal recessive genetic defect. Increased biotin breakdown was ruled out, as were artifacts of biotin supplementation and generalized defects in membrane permeability for biotin. These results provide evidence for a novel genetic defect in biotin transport. This child is the first known with this defect, which should now be included in the identified causes of biotin dependency.

Amidohydrolases↗