Familial hypercholestorolemia Flashcards
Familial hypercholesterolemia (FH) is a genetic disorder of ________ that is typified by considerable elevations in levels of ______________, from which patients are at an elevated risk for premature __________________
lipid metabolism
low- density lipoprotein cholesterol (LDL-C)
coronary heart disease (CHD).
The etiology of FH comprises of known mutations in the gene of the
- ____________
2.__________________________ gene - The gene of __________ (______)
- Rare mutations in ______________(____) gene.
LDL receptor (LDLR)
Proprotein convertase subtilisin/kexin type 9 (PCSK9)
apolipoprotein B (ApoB)
LDL receptor adapter protein 1 (LDLRAP1)
Epidemiology
______zygous FH (___FH) is the widely occurring form of the disease (prevalence of approximately 1 in ____ to _____ individuals globally and as high as 1 in ____ persons in some populations), with the preponderance of inheritance through _________________ mechanism.
Hetero; He
300 to 500
100
an autosomal-dominant
Epidemiology
_____zygous FH (___FH) on the other hand, is a very rare form of the disease (prevalence of 1 in ________ persons).
Homo; Ho
1 million
Epidemiology
However, some populations such as the French-Canadians, Lebanese (both in Brazil and Lebanon), Ashkenazi Jews, and Dutch Afrikaners, are at a significantly increased risk for FH owing to an augmented prevalence of __FH-associated mutations in the _____, in these so called “ _______ “ populations.
He
LDLR
founder
Clinical features of FH
Individuals with FH generally have drastically higher levels of _______ than most patients with severe hyperlipidemia.
LDL-C
Clinical features of FH
Case in point, subjects with FH above the age of 30 years often exhibit an LDL-C level of ____ milligrams per deciliter (mg/dL) (____ mmol/L) or higher;
patients between 20 and 29 years of age often exhibit LDL-C levels of _____ mg/dL ( ______ mmol/L) or higher;
while patients younger than 20 years of age often have an LDL-C level of ____ mg/dL (______ mmol/L) or higher
250; 13.9
220; 12.2
190; 10.5
high cholesterol levels more often than not , exhibit physical symptoms
T/F
F
Although high cholesterol levels more often than not do not exhibit any physical symptoms
cholesterol :These include, regions
•around the eyelids (_________________)
•as a ________ in front of the periphery of the iris ( __________)
•______ in the tendons of the hands and feet specifically the ______ ( _______ )
xanthelasma palpebrarum
white ring ; arcus senilis corneae
lumps; Achilles tendon ; tendon xanthoma
Risk factors for CVD in patients with FH
In HeFH, there is _________ gene and therefore, the disease condition is (more or less?) severe and (more or less ?) responsive to treatment such as _____ than HoFH.
one normally functioning
Less
More ; statins
Risk factors for CVD in patients with FH
The mean age for the inception of CVD in men with HeFH is ____ to ___ years and in women the onset occurs around ___ to —— years.
42 to 46
51 to 52
(HeFH or HoFH?) is an aggressive form of FH
HoFH
Risk factors for CVD in patients with FH cont’d
HoFH is frequently (responsive or unresponsive?) to conventional treatment for hypercholesterolemia owing to the patient’s —————————
unresponsive
lack of functional LDLR.
Risk factors for CVD in patients with FH cont’d
In patients with HoFH, the mean age at the time of diagnosis of CVD is _____ years.
Therefore, there is an ardent need for early diagnosis followed by aggressive therapeutic intervention and lifestyle modification.
20
The clinical diagnosis of FH is founded on ______________,_____________, and ______________
personal and family history, physical examination, and lipid concentrations.
Clinical diagnosis of FH
Three groups have developed clinical diagnostic tools for FH:
1. The _______ Program,
2. The ___________ Group in the ———-
3. The __________ Network
US MedPed
Simon Broome Register ; United Kingdom
Dutch Lipid Clinic
The Simon Broome criteria takes into consideration _________, ____ characteristics, _____ diagnosis, and _____, which include risk of fatal CHD in FH.
cholesterol concentrations
clinical
molecular
family history
2 Advantages of the Simon-Broome Criteria:
____________
____________
Ease of Remembrance
Economic viability
of the three criteria currently available, __________ is the most widely used by physicians.
the Simon-Broome Criteria
Disadvantage of the Simon-Broome Criteria
Simon-Broome criteria fails to differentiate between ___________ and ___________
It will also not discriminate between ________ and ________ such as secondary hypercholesterolemia, sitosterolemia, or other variants.
classical FH due to LDLR mutations and the other genetic origins of FH
FH and non-FH
Disadvantage of the Simon-Broome Criteria
More importantly, the criteria may overlook a _________, mainly those with a ________ and the _______ population in whom ________________________.
substantial proportion of FH patients
mild phenotype; pediatric
the phenotype has not yet emerged
In fact, a ____________ is the first presenting sign in many FH patients.
myocardial infarction
Disadvantage of the Simon-Broome Criteria
Additionally, the criteria does not allocate for understanding of ____________ correlations such as better response to _____ in ApoB-100 and ARH compared to LDLR mutations
known genotype-phenotype
statin therapy
The Dutch criteria for the diagnosis of FH are the modification of the US MEDPEB criteria.
T/F
F
Simon-Broome criteria
