- 著者
- Mariko Harada-Shiba Takao Ohta Akira Ohtake Masatsune Ogura Kazushige Dobashi Atsushi Nohara Shizuya Yamashita Koutaro Yokote Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia
- 出版者
- Japan Atherosclerosis Society
- 雑誌
- Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
- 巻号頁・発行日
- pp.CR002, (Released:2018-02-06)
- 参考文献数
- 49
- 被引用文献数
- 60
This paper describes consensus statement by Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia (FH) in order to improve prognosis of FH.FH is a common genetic disease caused by mutations in genes related to low density lipoprotein (LDL) receptor pathway. Because patients with FH have high LDL cholesterol (LDL-C) levels from the birth, atherosclerosis begins and develops during childhood which determines the prognosis. Therefore, in order to reduce their lifetime risk for cardiovascular disease, patients with FH need to be diagnosed as early as possible and appropriate treatment should be started.Diagnosis of pediatric heterozygous FH patients is made by LDL-C ≥140 mg/dL, and family history of FH or premature CAD. When the diagnosis is made, they need to improve their lifestyle including diet and exercise which sometimes are not enough to reduce LDL-C levels. For pediatric FH aged ≥10 years, pharmacotherapy needs to be considered if the LDL-C level is persistently above 180 mg/dL. Statins are the first line drugs starting from the lowest dose and are increased if necessary. The target LDL-C level should ideally be <140 mg/dL. Assessment of atherosclerosis is mainly performed by noninvasive methods such as ultrasound.For homozygous FH patients, the diagnosis is made by existence of skin xanthomas or tendon xanthomas from infancy, and untreated LDL-C levels are approximately twice those of heterozygous FH parents. The responsiveness to pharmacotherapy should be ascertained promptly and if the effect of treatment is not enough, LDL apheresis needs to be immediately initiated.
- 著者
- Mariko Harada-Shiba John J.P. Kastelein G. Kees Hovingh Kausik K. Ray Akira Ohtake Osamu Arisaka Takao Ohta Tomoo Okada Hideki Suganami Albert Wiegman
- 出版者
- Japan Atherosclerosis Society
- 雑誌
- Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
- 巻号頁・発行日
- pp.42242, (Released:2017-11-29)
- 参考文献数
- 24
- 被引用文献数
- 17
Aim: Children with Familial Hypercholesterolemia (FH) are widely prescribed statins, and it has been suggested that the effects of statins differ among ethnicities. We compared the efficacy and safety of pitavastatin in children and adolescents with FH in clinical trials conducted in Japan and Europe.
- 著者
- Yoshitsune Miyagi Mariko Harada-Shiba Takao Ohta
- 出版者
- 一般社団法人 日本動脈硬化学会
- 雑誌
- Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
- 巻号頁・発行日
- pp.31666, (Released:2015-10-27)
- 参考文献数
- 18
- 被引用文献数
- 4
Familial hypercholesterolemia (FH) is characterized by a high level of low-density lipoprotein cholesterol (LDL-C) and is inherited as an autosomal dominant trait. We report 4-year-old dichorionic diamniotic twins (boy and girl) with FH who presented with multiple xanthomas on the face, both knees, both feet, and buttocks. Family history revealed vertical transmission of hypercholesterolemia from father to patients, thereby suggesting dominant inheritance. Lipid data of their mother did not match the criteria of FH. However, lipid data of maternal grandmother and maternal sister matched the criteria of FH. LDL receptor gene analysis of the family revealed that their father was heterozygous for a missense mutation, L547V, their mother was heterozygous for a nonsense mutation, C675X, and patients were compound heterozygous for L547V and C675X. After 10 months of treatment with pitavastatin (2 mg/day) and ezetimibe (10 mg/day), LDL-C decreased from 595 mg/dL to 267 mg/dL in the boy and from 530 mg/dL to 182 mg/dL in the girl. These findings suggest that lipid-lowering therapy with statin may be considered in pediatric patients with compound heterozygous FH (hetero FH) before inducing LDL apheresis, and gene analysis for true diagnosis in pediatric patients with multiple xanthomas should be considered, though they appear to be hetero FH from the family history and lipid data of parents.
- 著者
- Mariko Harada-Shiba Hidenori Arai Shinichi Oikawa Takao Ohta Tomoo Okada Tomonori Okamura Atsushi Nohara Hideaki Bujo Koutaro Yokote Akihiko Wakatsuki Shun Ishibashi Shizuya Yamashita
- 出版者
- Japan Atherosclerosis Society
- 雑誌
- Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
- 巻号頁・発行日
- vol.19, no.12, pp.1043-1060, 2012 (Released:2012-12-20)
- 参考文献数
- 85
- 被引用文献数
- 144 145
Familial hypercholesterolemia (FH) is a highly prevalent autosomal dominant hereditary disease, generally characterized by three major signs, hyper-low-density-lipoprotein (LDL) cholesterolemia, tendon/skin xanthomas and premature coronary artery disease (CAD). Because the risk of CAD is very high in these patients, they should be identified at an early stage of their lives and started on intensive treatment to control LDL-cholesterol. We here introduce a new guideline for the management of FH patients in Japan intending to achieve better control to prevent CAD. Diagnostic criteria for heterozygous FH are 2 or more of 1) LDL-cholesterol ≥180 mg/dL, 2) tendon/skin xanthoma(s), and 3) family history of FH or premature CAD within second degree relatives, for adults; and to have both 1) LDL-cholesterol ≥140 mg/dL and 2) family history of FH or premature CAD within second degree relatives, for children. For the treatment of adult heterozygous FH, intensive lipid control with statins and other drugs is necessary. Other risks of CAD, such as smoking, diabetes mellitus, hypertension etc., should also be controlled strictly. Atherosclerosis in coronary, carotid, or peripheral arteries, the aorta and aortic valve should be screened periodically. FH in children, pregnant women, and women who wish to bear a child should be referred to specialists. For homozygotes and severe heterozygotes resistant to drug therapies, LDL apheresis should be performed. The treatment cost of homozygous FH is authorized to be covered under the program of Research on Measures against Intractable Diseases by the Japanese Ministry of Health, Labour, and Welfare.