USMLE® Step 1 style questions USMLE
A 21-year-old man comes to the emergency department because of acute-onset chest pain. The symptoms started less than an hour ago when the patient was walking up a flight of stairs. His father passed away from a myocardial infarction at 28-years-old. His temperature is 37.6°C (99.7°F), blood pressure is 117/75 mmHg, and pulse is 64/min. The patient appears anxious and in mild distress. Physical examination shows xanthomas bilaterally on the Achilles tendons. Laboratory testing is notable for a total serum cholesterol of 354 mg/dL. An electrocardiogram is ordered and the results are as follows:
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Which of the following conditions has the same inheritance pattern as this patient’s condition?
Content Reviewers:Viviana Popa, MD
With familial hypercholesterolemia, familial means the disease runs in families, so it has a genetic predisposition, hyper means excess and lastly cholesterolemia refers to the level of cholesterol in the blood.
But good and bad is overly simplistic, and like all things - the subtleties matter.
That’s why we want to keep LDL blood levels under control.
This is mainly done by the LDL receptors present on the surface of the liver cells.
First, the LDL molecules bind to the LDL receptors, which are clustered in specialized regions of the cell membrane called coated pits.
After binding, the coated pits along with the receptor-bound LDL are internalized by invagination, and they form coated vesicles inside the cell.
Next, the LDL receptor releases the LDL in the cytoplasm, and it gets recycled back to the cell surface.
At the same time, the coated vesicles fuse with an intracellular organelle called a lysosome.
Inside the lysosomes, LDL molecules are enzymatically degraded and free cholesterol molecules are released, which then cross the lysosomal membrane to enter the cytoplasm.
Now, in familial hypercholesterolaemia, mutations occur in the LDL receptor gene.
There are over 900 different types of mutations that can cause familial hypercholesterolemia - but luckily, they’ve been grouped into 5 major classes.
Class one mutations mainly affect the quantity of synthesized LDL receptors, so there are less available receptors to take up LDL from plasma.
Class two mutations affect the intracellular transport of LDL receptors back to the cell surface.
Class three mutations affect the binding of LDL to LDL receptors.
Familial hypercholesterolemia (FH) is an autosomal dominant condition in which there are abnormally high levels of LDL cholesterol in the blood. The condition increases a person’s risk for heart disease and other serious health problems. FH is caused by defects in one of several genes that control the amount of cholesterol in the blood. People with FH can present with xanthomas (fats build up under the skin), xanthelasma (fats build up in the eyelids), fatty liver, and pancreatitis.