caa a22 4500 46793309X CHVBK 20180406152949.0 cr unu---uuuuu 170328e20060401xx s 000 0 eng 10.1007/s10545-005-0243-2 doi (NATIONALLICENCE)springer-10.1007/s10545-005-0243-2 Clayton Peter Biochemistry, Endocrinology and Metabolism, Institute of Child Health, 30 Guilford St, WC1N 1 EH, London, UK aut B6-responsive disorders: A model of vitamin dependency [Elektronische Daten] [Peter Clayton] Summary: Pyridoxal phosphate is the cofactor for over 100 enzyme-catalysed reactions in the body, including many involved in the synthesis or catabolism of neurotransmitters. Inadequate levels of pyridoxal phosphate in the brain cause neurological dysfunction, particularly epilepsy. There are several different mechanisms that lead to an increased requirement for pyridoxine and/or pyridoxal phosphate. These include: (i) inborn errors affecting the pathways of B6 vitamer metabolism; (ii) inborn errors that lead to accumulation of small molecules that react with pyridoxal phosphate and inactivate it; (iii) drugs that react with pyridoxal phosphate; (iv) coeliac disease, which is thought to lead to malabsorption of B6 vitamers; (v) renal dialysis, which leads to increased losses of B6 vitamers from the circulation; (vi) drugs that affect the metabolism of B6 vitamers; and (vii) inborn errors affecting specific pyridoxal phosphate-dependent enzymes. The last show a very variable degree of pyridoxine responsiveness, from 90% in X-linked sideroblastic anaemia (δ-aminolevulinate synthase deficiency) through 50% in homocystinuria (cystathionine β-synthase deficiency) to 5% in ornithinaemia with gyrate atrophy (ornithine δ-aminotransferase deficiency). The possible role of pyridoxal phosphate as a chaperone during folding of nascent enzymes is discussed. High-dose pyridoxine or pyridoxal phosphate may have deleterious side-effects (particularly peripheral neuropathy with pyridoxine) and this must be considered in treatment regimes. None the less, in some patients, particularly infants with intractable epilepsy, treatment with pyridoxine or pyridoxal phosphate can be life-saving, and in other infants with inborn errors of metabolism B6 treatment can be extremely beneficial. SSIEM and Springer, 2006 Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/2-3(2006-04-01), 317-326 0141-8955 29:2-3<317 2006 29 10545 https://doi.org/10.1007/s10545-005-0243-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10545-005-0243-2 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Clayton Peter Biochemistry, Endocrinology and Metabolism, Institute of Child Health, 30 Guilford St, WC1N 1 EH, London, UK aut NATIONALLICENCE 773 0- Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/2-3(2006-04-01), 317-326 0141-8955 29:2-3<317 2006 29 10545 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer