When a "normal" cholesterol level is not normal: Exposing an unusual presentation of familial hypercholesterolemia

A classic finding in patients with familial hypercholesterolemia is the presence of markedly elevated levels of total and low-density lipoprotein cholesterol (LDL-C) with an LDL-C concentration of 190 mg/dL or greater. However, severe hypercholesterolemia is not inevitably present, and many patients who carry this diagnosis may have lower LDL-C levels. This case history describes a young woman whose mother and brother met clinical and genetic criteria for heterozygous familial hypercholesterolemia, but who had only a mild elevation in LDL-C, falling to <130 mg/dL after dietary intervention. Despite this finding, genetic testing revealed the presence of the same genetic variants as were noted in her mother and brother. In addition, a second genetic variant predisposing them to cholesterol gallstone formation was identified in all three family members. If genetic testing had not been performed, the diagnosis may have been missed or delayed, resulting in an increased risk for the vascular complications associated with familial hypercholesterolemia. This case supports the value of genetic testing of family members of those with familial hypercholesterolemia, even when LDL-C levels are not severely elevated.