Disease relevance of Metabolism, Inborn Errors

• Deficiency of STS (steryl-sulfatase; steryl-sulfate sulfohydrolase, EC 3.1.6.2) activity produces the syndrome of X chromosome-linked ichthyosis, which is one of the most common inborn errors of metabolism in man [1].
• Tyrosinase-negative oculocutaneous albinism (OCA) is one of classical inborn errors of metabolism, characterized by a complete lack of melanin pigments in the eyes and skin [2].
• These data suggest a possible therapeutic strategy encompassing the use of agmatine for the treatment of disturbed ureagenesis, whether secondary to inborn errors of metabolism or to liver disease [3].
• Hypotheses regarding the pathogenesis of the hepatotoxicity include preexisting mitochondrial disease or inborn errors of metabolism, VPA inhibition of beta-oxidation, and toxicity from VPA metabolites VPA, 4-ene-VPA, and 2,4-diene-VPA [4].
• As the classification suggests, there are many diffuse, or multifocal, brain disorders related to infantile spasms, e.g., inborn errors of metabolism, hypoxic-ischemic brain injury, and developmental brain defects such as tuberous sclerosis or Aicardi's syndrome [5].

High impact information on Metabolism, Inborn Errors

• A standard investigation for inborn errors of metabolism revealed that two patients had enzymatic defects of fatty acid oxidation, and the other two had partial deficiencies of ornithine transcarbamoylase [6].
• Mutations in many CYP genes cause inborn errors of metabolism and contribute to many clinically relevant diseases [7].
• Thus the urea cycle may serve as a model for the development of excretion pathways of toxic precursors which accumulate in inborn errors of metabolism [8].
• Steroid 21-hydroxylase deficiency is among the most common inborn errors of metabolism in man [9].
• Gas chromatography-mass spectrometry analysis revealed an accumulation of both diagnostic compounds in Delta hlyA culture supernatants, illustrating that the metabolic consequences of equivalent inborn errors of metabolism are conserved from fungi to humans [10].

Chemical compound and disease context of Metabolism, Inborn Errors

• The reduction in lactate in patients on valproate therapy may mask inborn errors of metabolism that normally result in an increase in blood lactate levels [11].
• BACKGROUND: The determination of organic acids and glycine conjugates in urine is key for the diagnosis and follow-up of several inborn errors of metabolism (IEM) [12].
• The method allows quantitative analysis of many compounds of interest in studies of inborn errors of metabolism, including betaine and dimethylglycine, which cannot be measured easily with other techniques [13].
• Several inborn errors of metabolism, as well as genetic animal models, are characterised by both elevated HDL cholesterol and increased rather than decreased cardiovascular risk [14].
• Impaired synthesis of adrenal steroid hormones because of steroid 21-hydroxylase deficiency is one of the most common inborn errors of metabolism [15].

Biological context of Metabolism, Inborn Errors

• At a threshold of 2 (in Z-score units), the sensitivity for a subgroup of inborn errors of metabolism (respiratory chain disorders) was 73%, 42%, and 31% for lactate, pyruvate, and the L/P ratio, respectively [16].
• Oxidative stress in inborn errors of metabolism: lessons from glutathione deficiency [17].
• Just as the discovery of 'inborn errors of metabolism' in humans contributed to our basic understanding of normal enzymatic pathways, so can genetic defects in signal transduction help to elucidate the functions normally subserved by different GPCR pathways [18].

Anatomical context of Metabolism, Inborn Errors

• Glial cells are primary targets of ammonia toxicity, which arises from liver disease or failure (such as from cirrhosis in alcoholics), urea cycle disorders, or inborn errors of metabolism [19].
• We here report 25 patients with nonmalignant disorders, ie, severe aplastic anemia (SAA, n = 12) or inborn errors of metabolism (IEM, n = 13), who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated high-resolution typed HLA-A, -B, and -DRbeta1 identical donors [20].

Gene context of Metabolism, Inborn Errors

• Mutations in GTP-cyclohydrolase I (GTP-CH) have been identified as causing a range of inborn errors of metabolism, including dopa-responsive dystonia [21].
• Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency are autosomal recessive inborn errors of metabolism with severe neurological symptoms resulting from a lack of sulfite oxidase activity [22].
• Our results confirm that MCAD is one of the more common inborn errors of metabolism [23].
• Although reductions in mGPD and PC may contribute to the abnormal insulin secretion present in overt diabetes, they are modest compared with the severe reductions seen in inherited inborn errors of metabolism [24].
• Molecular studies of genetic disorders affecting the expression of the human beta-globin gene: a model system for the analysis of inborn errors of metabolism [25].

Analytical, diagnostic and therapeutic context of Metabolism, Inborn Errors

• Tandem mass spectrometry: a new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism [26].
• The serum concentrations of beta-hydroxybutyrate and acetoacetate as well as the beta-hydroxybutyrate/acetoacetate ratio are important parameters for the differential diagnosis of certain inborn errors of metabolism [27].

References