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Half a Century Tales of Familial Hypercholesterolemia (FH) in Japan

View Article: PubMed Central - PubMed

ABSTRACT

Familial hypercholesterolemia (FH) is a disease characterized by a triad: elevated low-density lipoprotein (LDL) cholesterol, tendon xanthomas, and premature coronary heart disease. Thus, it can be considered as a model disease for hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD). For the diagnosis of hetero-FH, the detection of Achilles tendon xanthomas by palpation or on X-ray is an indispensable diagnostic skill in clinical lipidology. To prevent the under-diagnosis and under-treatment of FH, the diagnostic criteria should be more convenient and user-friendly. For a patient with cutaneous or tendon xanthomas, the probability of FH is very high; however, an absence of xanthoma does not rule out FH.

Brown and Goldstein elucidated the pathogenesis of FH by their work on LDL-receptor (LDL-R), for which they were awarded the Nobel Prize in 1985. In the 1950s, FH patients were divided into heterozygous (hetero-) and homozygous (homo-) FH, and diagnosing homo- and hetero-FH based on the phenotypic features of ASCVD or xanthomas frequently became difficult without the DNA analysis of FH genes. It is estimated that heterozygous mutations in the LDL-R or the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene will be found at a combined frequency of 0.005, which corresponds to 1/199 people in the general population in Japan.

Statins and anti-PCSK9 monoclonal antibodies are highly specific and efficient drugs for treating hetero- or homo-FH patients. Most clinical studies have reported an amelioration of ASCVD using long-term statin therapy. Clinical results using anti-PCSK9 monoclonal antibodies will emerge in a few years. In homo-FH patients, mipomersen and lomitapide are expected to yield good results. It is important to sequentially unravel the unrecognized pathogenetic mechanisms of FH to reduce its under-recognition and develop new management strategies for it.

No MeSH data available.


Related in: MedlinePlus

The first case of homo-FH in Japan was reported by Yamakawa and Kashiwabara in 1922. This 35-year-old man showed prominent generalized cutaneous and tendon xanthomatosis and severe ASCVD symptoms and signs due to hypercholesterolemia of 526 mg/dL.
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Figure 5: The first case of homo-FH in Japan was reported by Yamakawa and Kashiwabara in 1922. This 35-year-old man showed prominent generalized cutaneous and tendon xanthomatosis and severe ASCVD symptoms and signs due to hypercholesterolemia of 526 mg/dL.

Mentions: Familial hypercholesterolemia (FH) is a common genetic disease, which complicates atherosclerotic cardiovascular disease (ASCVD) because of high levels of low-density lipoprotein (LDL) cholesterol (LDL-C), and can thus be considered as a model disease for hypercholesterolemia and ASCVD1). The first case of FH reported by Fagge in 1873 was associated with cutaneous and tendon xanthomas (Figs. 1, 2, 3, and 4); however, the association of FH with ASCVD or hypercholesterolemia was unknown at that time2). The first homozygous FH (homo-FH) case in Japan was reported by Yamakawa and Kashiwabara in 19223). This 35-year-old man exhibited prominent generalized cutaneous xanthomatosis and severe ASCVD symptoms and signs due to hypercholesterolemia of 526 mg/dL (Fig. 5).


Half a Century Tales of Familial Hypercholesterolemia (FH) in Japan
The first case of homo-FH in Japan was reported by Yamakawa and Kashiwabara in 1922. This 35-year-old man showed prominent generalized cutaneous and tendon xanthomatosis and severe ASCVD symptoms and signs due to hypercholesterolemia of 526 mg/dL.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383536&req=5

Figure 5: The first case of homo-FH in Japan was reported by Yamakawa and Kashiwabara in 1922. This 35-year-old man showed prominent generalized cutaneous and tendon xanthomatosis and severe ASCVD symptoms and signs due to hypercholesterolemia of 526 mg/dL.
Mentions: Familial hypercholesterolemia (FH) is a common genetic disease, which complicates atherosclerotic cardiovascular disease (ASCVD) because of high levels of low-density lipoprotein (LDL) cholesterol (LDL-C), and can thus be considered as a model disease for hypercholesterolemia and ASCVD1). The first case of FH reported by Fagge in 1873 was associated with cutaneous and tendon xanthomas (Figs. 1, 2, 3, and 4); however, the association of FH with ASCVD or hypercholesterolemia was unknown at that time2). The first homozygous FH (homo-FH) case in Japan was reported by Yamakawa and Kashiwabara in 19223). This 35-year-old man exhibited prominent generalized cutaneous xanthomatosis and severe ASCVD symptoms and signs due to hypercholesterolemia of 526 mg/dL (Fig. 5).

View Article: PubMed Central - PubMed

ABSTRACT

Familial hypercholesterolemia (FH) is a disease characterized by a triad: elevated low-density lipoprotein (LDL) cholesterol, tendon xanthomas, and premature coronary heart disease. Thus, it can be considered as a model disease for hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD). For the diagnosis of hetero-FH, the detection of Achilles tendon xanthomas by palpation or on X-ray is an indispensable diagnostic skill in clinical lipidology. To prevent the under-diagnosis and under-treatment of FH, the diagnostic criteria should be more convenient and user-friendly. For a patient with cutaneous or tendon xanthomas, the probability of FH is very high; however, an absence of xanthoma does not rule out FH.

Brown and Goldstein elucidated the pathogenesis of FH by their work on LDL-receptor (LDL-R), for which they were awarded the Nobel Prize in 1985. In the 1950s, FH patients were divided into heterozygous (hetero-) and homozygous (homo-) FH, and diagnosing homo- and hetero-FH based on the phenotypic features of ASCVD or xanthomas frequently became difficult without the DNA analysis of FH genes. It is estimated that heterozygous mutations in the LDL-R or the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene will be found at a combined frequency of 0.005, which corresponds to 1/199 people in the general population in Japan.

Statins and anti-PCSK9 monoclonal antibodies are highly specific and efficient drugs for treating hetero- or homo-FH patients. Most clinical studies have reported an amelioration of ASCVD using long-term statin therapy. Clinical results using anti-PCSK9 monoclonal antibodies will emerge in a few years. In homo-FH patients, mipomersen and lomitapide are expected to yield good results. It is important to sequentially unravel the unrecognized pathogenetic mechanisms of FH to reduce its under-recognition and develop new management strategies for it.

No MeSH data available.


Related in: MedlinePlus