caa a22 4500 475786300 CHVBK 20180406123659.0 cr unu---uuuuu 170329e20000101xx s 000 0 eng 10.1007/s004310050004 doi (NATIONALLICENCE)springer-10.1007/s004310050004 Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency [Elektronische Daten] [O. Sakamoto, Y. Suzuki, X. Li, Y. Aoki, M. Hiratsuka, E. Holme, J. Kudoh, N. Shimizu, K. Narisawa] Holocarboxylase synthetase (HCS) deficiency is a disorder of biotin metabolism characterised by metabolic ketoacidosis and skin lesions due to reduced activities of multiple biotin-dependent carboxylases. The onset of this disease is usually between the neonatal and infantile period. Here we report the molecular analysis of an atypical case of HCS deficiency, where the patient developed his first episode of acidosis at age 8 years and had an exceptionally slow response to biotin therapy. A homozygous mutation was identified at the +5 position of the splice donor site in intron 10 of the HCS gene (IVs10 + 5(g → a)), resulting in abnormal splicing of HCS mRNA. A moderate decrease in the amount of normal HCS mRNA may account for the atypical, late-onset phenotype of this patient. Conclusion Molecular analysis is a useful tool for understanding the phenotypic variations in holocarboxylase synthetase deficiency. Springer-Verlag Berlin Heidelberg, 2000 Key words Biotin nationallicence Holocarboxylase synthetase nationallicence Multiple carboxylase deficiency nationallicence Splice error nationallicence Sakamoto O. Department of Medical Genetics (Biochemical Genetics), Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan, e-mail: ysuzuki@mail.cc.tohoku.ac.jp, Tel.: +81-22-717-8140, Fax: +81-22-717-8142, JP aut Suzuki Y. Department of Medical Genetics (Biochemical Genetics), Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan, e-mail: ysuzuki@mail.cc.tohoku.ac.jp, Tel.: +81-22-717-8140, Fax: +81-22-717-8142, JP aut Li X. Department of Medical Genetics (Biochemical Genetics), Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan, e-mail: ysuzuki@mail.cc.tohoku.ac.jp, Tel.: +81-22-717-8140, Fax: +81-22-717-8142, JP aut Aoki Y. Department of Medical Genetics (Biochemical Genetics), Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan, e-mail: ysuzuki@mail.cc.tohoku.ac.jp, Tel.: +81-22-717-8140, Fax: +81-22-717-8142, JP aut Hiratsuka M. Department of Medical Genetics (Biochemical Genetics), Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan, e-mail: ysuzuki@mail.cc.tohoku.ac.jp, Tel.: +81-22-717-8140, Fax: +81-22-717-8142, JP aut Holme E. Department of Clinical Chemistry, Gothenburg University, Sahlgen's Hospital, Gothenburg, Sweden, SE aut Kudoh J. Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan, JP aut Shimizu N. Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan, JP aut Narisawa K. Department of Medical Genetics (Biochemical Genetics), Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan, e-mail: ysuzuki@mail.cc.tohoku.ac.jp, Tel.: +81-22-717-8140, Fax: +81-22-717-8142, JP aut https://doi.org/10.1007/s004310050004 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s004310050004 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sakamoto O. Department of Medical Genetics (Biochemical Genetics), Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan, e-mail: ysuzuki@mail.cc.tohoku.ac.jp, Tel.: +81-22-717-8140, Fax: +81-22-717-8142, JP aut NATIONALLICENCE 700 1- Suzuki Y. Department of Medical Genetics (Biochemical Genetics), Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan, e-mail: ysuzuki@mail.cc.tohoku.ac.jp, Tel.: +81-22-717-8140, Fax: +81-22-717-8142, JP aut NATIONALLICENCE 700 1- Li X. Department of Medical Genetics (Biochemical Genetics), Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan, e-mail: ysuzuki@mail.cc.tohoku.ac.jp, Tel.: +81-22-717-8140, Fax: +81-22-717-8142, JP aut NATIONALLICENCE 700 1- Aoki Y. Department of Medical Genetics (Biochemical Genetics), Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan, e-mail: ysuzuki@mail.cc.tohoku.ac.jp, Tel.: +81-22-717-8140, Fax: +81-22-717-8142, JP aut NATIONALLICENCE 700 1- Hiratsuka M. Department of Medical Genetics (Biochemical Genetics), Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan, e-mail: ysuzuki@mail.cc.tohoku.ac.jp, Tel.: +81-22-717-8140, Fax: +81-22-717-8142, JP aut NATIONALLICENCE 700 1- Holme E. Department of Clinical Chemistry, Gothenburg University, Sahlgen's Hospital, Gothenburg, Sweden, SE aut NATIONALLICENCE 700 1- Kudoh J. Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan, JP aut NATIONALLICENCE 700 1- Shimizu N. Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan, JP aut NATIONALLICENCE 700 1- Narisawa K. Department of Medical Genetics (Biochemical Genetics), Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan, e-mail: ysuzuki@mail.cc.tohoku.ac.jp, Tel.: +81-22-717-8140, Fax: +81-22-717-8142, JP aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer