JIMD Reports, Volume 21 pp 115-122

Part of the JIMD Reports book series (JIMD, volume 21) | Cite as

Infantile Cases of Sitosterolaemia with Novel Mutations in the ABCG5 Gene: Extreme Hypercholesterolaemia is Exacerbated by Breastfeeding

  • Hayato Tada
  • Masa-aki Kawashiri
  • Mutsuko Takata
  • Kunihiro Matsunami
  • Atsushi Imamura
  • Misayo Matsuyama
  • Hirotake Sawada
  • Hiroyuki Nunoi
  • Tetsuo Konno
  • Kenshi Hayashi
  • Atsushi Nohara
  • Akihiro Inazu
  • Junji Kobayashi
  • Hiroshi Mabuchi
  • Masakazu Yamagishi
Case Report

Abstract

Few data exists regarding the clinical impact of breastfeeding in infantile sitosterolaemic cases. We report four Japanese infantile cases of sitosterolaemia, an extremely rare inherited disease characterised by increased serum levels of plant sitosterol, presenting with severe hypercholesterolaemia and systemic xanthomas exacerbated by breastfeeding. In these four cases, genetic analyses were performed for low-density lipoprotein (LDL) receptor, proprotein convertase subtilisin/kexin type 9 (PCSK9), LDL receptor adaptor protein 1 and ATP-binding cassette (ABC) subfamily G member 5 and 8 (ABCG5 and ABCG8) genes. We assessed their clinical manifestations, including responsiveness to a variety of treatments, especially to weaning from breastfeeding and use of ezetimibe. Two pairs of mutations in the ABCG5 gene in each case, including two novel mutations (c.130C>T or p.Ser44Ala and c.1813_1817delCTTTT or p.Pro558GlufsX14) and two known mutations (c.1306G>A or p.Arg389His and c.1336C>T or p.Arg446X), were identified. Significant reductions in cholesterol levels were obtained by means of weaning from breastfeeding alone. Substantial reductions in sitosterol levels, without any apparent side effects, were observed with ezetimibe. In conclusion, we have identified infantile Japanese sitosterolaemic subjects with extreme hypercholesterolaemia exacerbated by breastfeeding. Their unique response to weaning from breastfeeding, as well as to use of ezetimibe, could provide insights into the metabolic basis of sterols in humans.

Keywords

ABCG5 ABCG8 Ezetimibe Familial hypercholesterolaemia Sitosterolaemia 

Supplementary material

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(DOC 148 kb)
337732_1_En_404_MOESM2_ESM.pptx (1.1 mb)
(DOCX 1126 kb)

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Hayato Tada
    • 1
  • Masa-aki Kawashiri
    • 1
  • Mutsuko Takata
    • 2
  • Kunihiro Matsunami
    • 3
  • Atsushi Imamura
    • 3
  • Misayo Matsuyama
    • 4
  • Hirotake Sawada
    • 4
  • Hiroyuki Nunoi
    • 4
  • Tetsuo Konno
    • 1
  • Kenshi Hayashi
    • 1
  • Atsushi Nohara
    • 5
  • Akihiro Inazu
    • 6
  • Junji Kobayashi
    • 7
  • Hiroshi Mabuchi
    • 5
  • Masakazu Yamagishi
    • 1
  1. 1.Division of Cardiovascular MedicineKanazawa University Graduate School of MedicineKanazawaJapan
  2. 2.Department of Internal MedicineKomatsu Municipal HospitalKomatsuJapan
  3. 3.Department of PediatricsGifu Prefectural General Medical CenterGifuJapan
  4. 4.Division of Pediatrics, Department of Reproductive and Developmental Medicine, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan
  5. 5.Department of Lipidology, Graduate School of Medical ScienceKanazawa UniversityKanazawaJapan
  6. 6.Department of Laboratory Science, Molecular Biochemistry and Molecular Biology, Graduate School of Medical ScienceKanazawa UniversityKanazawaJapan
  7. 7.Department of General MedicineKanazawa Medical UniversityUchinadaJapan

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