caa a22 4500 46793259X CHVBK 20180406152947.0 cr unu---uuuuu 170328e20060201xx s 000 0 eng 10.1007/s10545-006-0214-2 doi (NATIONALLICENCE)springer-10.1007/s10545-006-0214-2 Refining the diagnosis of mitochondrial HMG-CoA synthase deficiency [Elektronische Daten] [R. Aledo, C. Mir, R. Dalton, C. Turner, J. Pié, F. Hegardt, N. Casals, M. Champion] Summary: Mitochondrial HMG-CoA synthase deficiency is an inherited metabolic disorder caused by a defect in the enzyme that regulates the formation of ketone bodies. Patients present with hypoketotic hypoglycaemia, encephalopathy and hepatomegaly, usually precipitated by an intercurrent infection or prolonged fasting. The diagnosis may easily be missed as previously reported results of routine metabolic investigations, urinary organic acids and plasma acylcarnitines may be nonspecific or normal, and a high index of suspicion is required to proceed to further confirmatory tests. We describe a further acute case in which the combination of urinary organic acids, low free carnitine and changes in the plasma acylcarnitine profile on carnitine supplementation were very suggestive of a defect in ketone synthesis. The diagnosis of mitochondrial HMG-CoA synthase deficiency was confirmed on genotyping, revealing two novel mutations: c.614G > A (R188H) and c.971T > C (M307T). A further sibling, in whom the diagnosis had not been made acutely, was also found to be affected. The possible effects of these mutations on enzyme activity are discussed. SSIEM and Springer, 2006 Aledo R. Unit of Biochemistry and Molecular Biology, School of Health Sciences, International University of Catalonia, Spain aut Mir C. Unit of Biochemistry and Molecular Biology, School of Health Sciences, International University of Catalonia, Spain aut Dalton R. Wellchild Trust Research Laboratory, Guy's Hospital, London, UK aut Turner C. Wellchild Trust Research Laboratory, Guy's Hospital, London, UK aut Pié J. Department of Pharmacology and Physiology, School of Medicine, University of Zaragoza, Spain aut Hegardt F. Department of Biochemistry and Molecular Biology, University of Barcelona, School of Pharmacy, Barcelona, Spain aut Casals N. Unit of Biochemistry and Molecular Biology, School of Health Sciences, International University of Catalonia, Spain aut Champion M. Department of Paediatric Metabolic Medicine, Level 6-Sky, Evelina Children's Hospital, St Thomas Hospital, Lambeth Palace Road, SE1 7EH, London, UK aut Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/1(2006-02-01), 207-211 0141-8955 29:1<207 2006 29 10545 https://doi.org/10.1007/s10545-006-0214-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10545-006-0214-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Aledo R. Unit of Biochemistry and Molecular Biology, School of Health Sciences, International University of Catalonia, Spain aut NATIONALLICENCE 700 1- Mir C. Unit of Biochemistry and Molecular Biology, School of Health Sciences, International University of Catalonia, Spain aut NATIONALLICENCE 700 1- Dalton R. Wellchild Trust Research Laboratory, Guy's Hospital, London, UK aut NATIONALLICENCE 700 1- Turner C. Wellchild Trust Research Laboratory, Guy's Hospital, London, UK aut NATIONALLICENCE 700 1- Pié J. Department of Pharmacology and Physiology, School of Medicine, University of Zaragoza, Spain aut NATIONALLICENCE 700 1- Hegardt F. Department of Biochemistry and Molecular Biology, University of Barcelona, School of Pharmacy, Barcelona, Spain aut NATIONALLICENCE 700 1- Casals N. Unit of Biochemistry and Molecular Biology, School of Health Sciences, International University of Catalonia, Spain aut NATIONALLICENCE 700 1- Champion M. Department of Paediatric Metabolic Medicine, Level 6-Sky, Evelina Children's Hospital, St Thomas Hospital, Lambeth Palace Road, SE1 7EH, London, UK aut NATIONALLICENCE 773 0- Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/1(2006-02-01), 207-211 0141-8955 29:1<207 2006 29 10545 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer