가족성 고콜레스테롤혈증, 정의, Familial hypercholesterolaemia, definition

 

가족성 고콜레스테롤혈증(FH)은 가장 흔한 상염색체 우성 유전 질환입니다. 임상 증후군(표현형)은 매우 높은 수준의 저밀도 지단백질 콜레스테롤(LDL-C) 및 조기 발병 동맥 경화성 심혈관 질환의 경향을 특징으로 합니다. Homozygotes는 일반적으로 어린 시절에 질병을 나타냅니다.

 

문헌에는 FH에 대한 여러 정의가 있습니다. 일부는 유전자 검사 시행을 요구하는 반면 다른 것들은 다른 임상적 특성이 있거나/없는 매우 높은 수준의 LDL-C를 요구합니다.

 

DEFINITIONS

가족성 고콜레스테롤혈증(FH)은 저밀도 지단백질 콜레스테롤(LDL-C) 이화작용(catabolism)에 중요한 유전자 중 하나의 돌연변이에 의해 야기되는 유전병입니다. FH 임상 증후군 또는 표현형은 임상 기준에 의해 정의되며, 어떤 치료가 제공되는지 결정하는 것은 증후군의 중증도입니다. 임상적 정의는 사용 목적에 따라 약간 다릅니다. 다음의 세 가지 임상 정의는 가장 일반적으로 사용됩니다.

 

● Dutch Lipid Clinic

Dutch Lipid Clinic Network diagnostic criteria for familial hypercholesterolaemia

 

Criteria	Points
1) Family history
First-degree relative with known premature (men: <55 years; women: <60 years) coronary or vascular disease, or First-degree relative with known LDL-C above the 95th percentile	1
First-degree relative with tendinous xanthomata and/or arcus cornealis, or Children <18 years of age with LDL-C above the 95th percentile	2
2) Clinical history
Patient with premature (men: <55 years; women: <60 years) coronary artery disease	2
Patient with premature (men: <55 years; women: <60 years) cerebral or peripheral vascular disease	1
3) Physical examination
Tendinous xanthomata	6
Arcus cornealis before age 45 years	4
4) LDL-C levels
LDL-C ≥8.5 mmol/L (325 mg/dL)	8
LDL-C 6.5-8.4 mmol/L (251-325 mg/dL)	5
LDL-C 5.0-6.4 mmol/L (191-250 mg/dL)	3
LDL-C 4.0-4.9 mmol/L (155-190 mg/dL)	1
5) DNA analysis
Functional mutation in the LDLR, apoB, or PCSK9 gene	8
Choose only one score per group, the highest applicable diagnosis (diagnosis is based on the total number of points obtained) A "definite" FH diagnosis requires >8 points A "probable" FH diagnosis requires 6-8 points A "possible" FH diagnosis requires 3-5 points

 

FH: familial hypercholesterolaemia; LDL-C: low-density lipoprotein-cholesterol.

* Exclusive of each other (ie, maximum six points if both are

 

Reprinted from: Familial hypercholesterolaemia (‎FH)‎ : report of a second WHO consultation, Geneva, 4 September 1998. World Health Organization, p. 13, Copyright © 1998. Available at: http://apps.who.int/iris/handle/10665/66346 (Accessed on April 9, 2013).

 

● Simon Broome

Simon Broome Familial Hypercholesterolemia Register diagnostic criteria for familial hypercholesterolemia[1-3]

 

Criteria	Description
a	Total cholesterol concentration above 7.5 mmol/liter (290 mg/dL) in adults or a total cholesterol concentration above 6.7 mmol/liter (259 mg/dL) in children aged less than 16 years, or
	Low density lipoprotein cholesterol concentration above 4.9 mmol/liter (189 mg/dL) in adults or above 4.0 mmol/liter (155 mg/dL) in children
b	Tendinous xanthomata in the patient or a first-degree relative
c	DNA-based evidence of mutation in the LDLR, PCSK9, or APOB gene
d	Family history of myocardial infarction before age 50 years in a second-degree relative or before age 60 years in a first-degree relative
e	Family history of raised total cholesterol concentration above 7.5 mmol/liter (290 mg/dL) in a first- or second-degree relative

 

A "definite" FH diagnosis requires either criteria a and b, or criterion c. A "probable" FH diagnosis requires either criteria a and d, or criteria a and e.

FH: familial hypercholesterolemia.

 

References:

Risk of fatal coronary heart disease in familial hypercholesterolemia. Scientific Steering Committee on behalf of the Simon Broome Register Group. BMJ 1991; 303:893.

Mortality in treated heterozygous familial hypercholesterolemia: implications for clinical management. Scientific Steering Committee on behalf of the Simon Broome Register Group. Atherosclerosis 1999; 142:105.

National Collaborating Centre for Primary Care (UK). Identification and Management of Familial Hypercholesterolaemia (FH) [Internet]. London: Royal College of General Practitioners (UK); 2008 Aug. (NICE Clinical Guidelines, No. 71.) Appendix F, Simon Broome Diagnostic criteria for index individuals and relatives. Available from: https://www.ncbi.nlm.nih.gov/books/NBK53810/

Reproduced from: Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. Am J Epidemiol 2004; 160(5):407-420. By permission of Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. Copyright © 2017.

 

● American Heart Association criteria for the clinical diagnosis of FH : 저밀도 지단백질 콜레스테롤 (LDL-C)> 190 mg/dL이면서 LDL-C > 190 mg / dL인 first degree relative 또는 알려진 조기 관상 동맥 심장 질환(남성 < 55 세; 여성 < 60 세)

 

REF. UpToDate 2019.08.23