Familial+hypercholesterolemia





Discovery of FH
Familial Hypercholesterolemia, or FH, was discovered in the 1970’s and 1980’s by two scientist, Joseph Goldstein and Dr Michael Brown, at the University of Texas Southwestern Medical Center in Dallas. These two scientists were only able to discover FH after the discovery of the lipoprotein LDL. Michael and Goldstein performed several experiments using HMG CoA, or an enzyme that slows the production of cholesterol, in order to measure the activity of the enzyme and the levels of LDL in the blood. HMG CoA stops working after LDL is added to the serum. In their experiments, the two scientists used blood samples from both people who were homozygous dominant for FH and people who did not have FH. In one of their many experiments, they hypothesized that the defect was in the gene that codes for HMG CoA, because in the people with FH, even when LDL was present HMG CoA would still be at work. Although the evidence was compelling, it was quickly disapproved after additional testing that revealed that the defect was in the LDL receptor. The LDL receptors are responsible for stopping HMG CoA from working, and because of the defect, they could not fulfill their function.

= What is Familial Hypercholesterolemia? =

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Familial Hypercholesterolemia, also know as FH, is a genetic disorder caused by a mutation in chromosome 19. The inheritance pattern of the gene is that of autosomal dominance, meaning that if someone has FH, their children will have a 50% chance of inheritance . The disorder is caused by a genetic mutation and not a chromosomal mutation. The gene involved is the LDLR gene that provide the instructions for creating the receptors for low-density lipoproteins, or LDL. The LDL receptors are responsible for transferring 70% of the LDL cholesterol, or LDL-C, from our blood stream into the liver. In patients with FH, the poor functionality of LDL receptors causes a lack of LDL-C uptake into the liver, and a high concentration of LDL-C in the blood stream. The high levels of LDL-C in the circulation forces non-hepatic cells, or non liver cells, to absorb the excess LDL-C through cholesterol scavenger pathways. It is especially bad when LDL-C is absorbed into monocyte/macrophages in the arterial intima, also known as the cells that make up the inner layer in blood vessels and arteries.  Once the LDL-C is taken in by these cells, the monocyte/macrophages transform into foam cells that deposit throughout the body. These cholesterol deposits, or xanthomas, can occur in the <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">skin, cornea, heart valves, and other places that can lead to damage in the arteries. ======



<span style="background-color: #ffffff; color: #642a8f; font-family: &#39;Bree Serif&#39;; font-size: 24pt; vertical-align: baseline;">Symptoms
<span style="background-color: #ffffff; color: #0b5394; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">Familial Hypercholesterolemia includes symptoms such as:
 * <span style="background-color: #ffffff; color: #231f20; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">xanthomas, or cholesterol deposits around tendons, on the elbows, knees, and buttocks.
 * <span style="background-color: #ffffff; color: #231f20; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">xanthelasmas, or cholesterol deposits that occur around the eyes.
 * <span style="background-color: #ffffff; color: #231f20; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">corneal arcus, or grayish-white cholesterol deposits around the corneas.
 * <span style="background-color: #ffffff; color: #231f20; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">Any chest pain accompanied with physical activity.

<span style="background-color: #ffffff; color: #642a8f; font-family: &#39;Bree Serif&#39;; font-size: 24pt; vertical-align: baseline;">Diagnosis
<span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">FH is an inherited condition, as their is a 50% chance that parents who have the disorder will pass the condition down to their children. Even is a child is not exhibiting symptoms of FH, if you have a family history of the disorder, it is crucial that you get him/her checked out at a young age. In order to make an accurate diagnosis, doctors will first conduct a physical exam to search for any xanthomas and lesions. In addition, a blood sample will be drawn and analyzed for any raised levels of LDL and cholesterol. In children, a person with FH will have cholesterol levels that are higher than 260 mg/dL, and in adults it would be anything above 290 mg/dL. Also, a diagnosis can be made based on the concentration of LDL-C in the blood. In adults, LDL levels higher than 190 mg/dL suggest that they have FH, and in children, it is higher that 155 mg/dL.

<span style="background-color: #ffffff; color: #0b5394; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">The symptoms that come with FH can be treated through changes in lifestyle and diet such as:


 * <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">Decrease consumption of red meat
 * <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">Increase consumption of lean proteins
 * <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">Switch to low-fat dairy
 * <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">Add Fruits, vegetables, and nuts into your diet
 * <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">No sweetened drinks or soda
 * <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">Limit alcohol intake to no more than two drinks a day for men and one for women
 * <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 24px;">No smoking
 * <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 24px;">Sleep regularly

<span style="background-color: #ffffff; color: #0b5394; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">FH can also be treated through medication that reduces LDL-cholesterol, such as:
 * <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">simvastatin
 * <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 24px;">lovastatin
 * <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 24px;">atorvastatin
 * <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 24px;">fluvastatin
 * <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 24px;">rosuvastatin

<span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">In people with FH, diet and exercise are important to maintain in order to keep a healthy weight, which can lower the levels of cholesterol in their blody.

<span style="background-color: #ffffff; color: #642a8f; font-family: &#39;Times New Roman&#39;; font-size: 24pt; vertical-align: baseline;">How Common Is It?

<span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">FH occurs in 1 in 250 people, and fewer than 10% of the individuals with the condition are actually diagnosed with the FH. The disorder is more common in certain ethnicities such as, French Canadian, Jewish Ashkenazi, South African Afrikaners, Tunisian, and Christian Lebanese.

<span style="background-color: #ffffff; color: #642a8f; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">Glossary <span style="background-color: #ffffff; color: #0b5394; font-family: &#39;Times New Roman&#39;; font-size: 12pt; vertical-align: baseline;">Cholesterol- <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 12pt; vertical-align: baseline;">a compound of the sterol type found in most body tissues. Cholesterol and its derivatives are important constituents of cell membranes and precursors of other steroid compounds, but a high proportion in the blood of low-density lipoprotein (which transports cholesterol to the tissues) is associated with an increased risk of coronary heart disease. <span style="background-color: #ffffff; color: #0b5394; font-family: &#39;Times New Roman&#39;; font-size: 12pt; vertical-align: baseline;">Receptor- <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 12pt; vertical-align: baseline;">an organ or cell able to respond to light, heat, or other external stimulus and transmit a signal to a sensory nerve. <span style="background-color: #ffffff; color: #0b5394; font-family: &#39;Times New Roman&#39;; font-size: 12pt; vertical-align: baseline;">Enzyme- <span style="background-color: #ffffff; font-family: &#39;Times New Roman&#39;; font-size: 12pt; vertical-align: baseline;">a substance produced by a living organism that acts as a catalyst to bring about a specific biochemical reaction.

<span style="background-color: #ffffff; color: #642a8f; font-family: &#39;Times New Roman&#39;; font-size: 18pt; vertical-align: baseline;">Citation <span style="background-color: #ffffff; color: #1155cc; font-family: &#39;Times New Roman&#39;; font-size: 12pt; vertical-align: baseline;">[|https://www.healthline.com/health/familial-hypercholesterolemia#symptoms] <span style="background-color: #ffffff; color: #1155cc; font-family: &#39;Times New Roman&#39;; font-size: 12pt; vertical-align: baseline;">[] <span style="background-color: #ffffff; color: #1155cc; font-family: &#39;Times New Roman&#39;; font-size: 12pt; vertical-align: baseline;">[] <span style="background-color: #ffffff; color: #1155cc; font-family: &#39;Times New Roman&#39;; font-size: 12pt; vertical-align: baseline;">[|https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2740366/#R6] <span style="background-color: #ffffff; color: #1155cc; font-family: &#39;Times New Roman&#39;; font-size: 12pt; vertical-align: baseline;">[] <span style="background-color: #ffffff; color: #1155cc; font-family: &#39;Times New Roman&#39;; font-size: 12pt; vertical-align: baseline;">[|https://www.genome.gov/25520184/learning-about-familial-hypercholesterolemia]