Question

Case 3 A 20-year old, female presents to the dermatologist with complaints of multiple, small to large (2 mm to 3 cm) soft, asymptomatic yellow colored nodular lesions all over the body since the age of 2 years. She was subsequently referred for biochemical investigations, where an altered lipid profile was noticed. A detailed history from the parents revealed that the patient developed the swellings since the age of 2 years, which gradually increased to the present size. At the age of 3 years, patient was treated by a local doctor but the symptoms did not subside. There is no history of chest pain, breathlessness, hypertension, diabetes mellitus, or any other chronic illness. Family history: Maternal side shows history of sudden deaths at a young age (36-44 years) (Mother's elder brother and all his 3 sons have died at an early age due to possible myocardial infarction) Lipid profile of the patient: Total cholesterol (mg/dl) 580 Triglycerides (mg/dl) 134 LDL (mg/dl) 460 HDL (mg/dl) 93 VLDL (mg/dl) 27 LDL/HDL ratio 4.94 Please describe a potential underlying mechanism for the elevated cholesterol levels found in this individual Triglycerides are within normal values in this individual. Describe how triglyceride levels would be normal but cholesterol levels could be elevated in this individual

Answer 1

This individual is having a strong family history of deaths at an early age due to possible Myocardial Infarction. Hence, the potential underlying mechanism for elevated cholesterol levels found in this client is the Familial Hypercholesterolemia (inherited form of high cholesterol) since the symptoms started as early as 2 years of age.

The cause of familial hypercholesterolaemia is the mutation in a gene. Normally, LDL cholesterol attach to ‘receptor’ sites on the targeted cells and are then absorbed. The LDLR gene, which is on chromosome 19, controls the production of these receptors. Mutation of the LDLR gene changes the way the receptors develop, either in number or structure and thus cholesterol is not well absorbed into cells, and remains circulating in the blood which leads to elevated cholesterol and LDL levels. Less commonly, familial hypercholesterolemia is caused by a mutation on other genes, such as APOB or PCSK9.

If the individual gets mutated gene from one parent, as in this case, it's called Heterozygous Familial Hypercholesterolemia. They will have half of their functioning LDL receptors. Individuals who get a malfunctioning gene from both parents don't have any functioning LDL receptors. This is called Homozygous Familial Hypercholesterolemia.

Elevated levels of Triglycerides in the blood is usually through the dietary consumption of high saturated fats and trans fats. Consumption of foods high in carbohydrates also elevates triglycerides. Excessive alcohol intake also may elevate triglyceride level. Triglyceride levels can become high as a reaction to having kidney diseases, hypothyroidism and diabetes. In the given individual, there is no history of any of these diseases or excessive intake of saturated fats or high carbohydrates. That is the reason for having a normal triglyceride level, while having an elevated cholesterol level due to Familial Hypercholesterolemia.