Familial hypercholesterolemia

Abstract

A 5-year-old girl born out of nonconsanguineous marriage presented with yellow-white extensive flat-topped lesions over both buttocks suggestive of xanthomas, which were present for the last 1 year. There was no history of shortness of breath or chest pain. The father had tendon xanthomas over both tendon Achilles. Her mother had no such lesions. Her paternal grandfather died of stroke at the age of 55 years. There was no history of atherosclerotic cardiovascular disease(ASCVD) in the other family members. On examination, the girl was healthy-looking with large xanthomas over both buttocks [Figure 1a]. She did not have any tendon xanthomas or xanthelasma. All her pulses were equally palpable, and the cardiac examination was essentially normal. Her father had tendon xanthomas over both ankle joints [Figure 1b]. Investigations revealed total cholesterol of 913 mg/dl, serum triglyceride (TG) 158 mg/dl, serum low-density lipoprotein (LDL) 695 mg/dl, and serum high-density lipoprotein (HDL) 66 mg/dl. Her father had total cholesterol of 355 mg/dl, serum TG 122 mg/dl, LDL 246 mg/dl, and HDL 49 mg/dl. Her mother had total cholesterol of 324 mg/dl, serum TG 110 mg/dl, LDL 220 mg/dl, and HDL 51 mg/dl. Electrocardiography and echocardiography were essentially normal for the girl. The provisional diagnosis was familial hypercholesterolemia which was confirmed by clinical exome sequencing, The final diagnosis was familial hypercholesterolemia type 1. The culprit mutation was a homozygous variant c. 666C>A (p.cys222Ter) on exon 7 of chromosome 19. The patient and both her parents were initiated on tablet atorvastatin 20 mg once daily at bedtime. At 3 months, her lipid profile was still deranged. Hence, atorvastatin was increased to 40 mg once daily and tablet ezetimibe 10 mg once daily was also added. At last follow-up, her cholesterol was 770 mg/dl, TG 104 mg/dl, LDL 593 mg/dl, and HDL 61 mg/dl.Figure 1: The child with flat yellowish xanthomas over both buttocks (a), the father with tendon xanthomas over both Achilles tendons (b)Homozygous familial hypercholesterolemia is a disorder of lipoprotein metabolism caused by mutations in the LDL receptor gene, leading to an absence of functional receptors on the cell membrane, causing decreased uptake of LDL into the liver from blood, resulting in increased levels of LDL-cholesterol (LDL-C). In 1939, familial hypercholesterolemia was first described by Muller.[1] In cases with familial hypercholesterolemia, high cholesterol may manifest as xanthomas on the eyelids, tendons of the elbows, knees, hands, and feet.[2] The diagnosis in our case was made based on Simon Broome Register criteria.[3] Treatment is often difficult despite advances in lipid-lowering therapies.[4] The 2019 ESC/EAS Guidelines for the Management of Dyslipidemias suggests that statin treatment should be initiated as early as 6–10 years of age along with healthy lifestyle measure. Proprotein convertase subtisilin/kexin type 9 (PCSK9) inhibitors can be used in some of the children with homozygous familial hypercholesterolemia; however, it would likely be ineffective in our patient as she is harboring LDL-null mutation. Recommended goals for children >10 years of age are LDL-C <3.5 mmol/l (135 mg/dl) or at least a 50% reduction from the baseline. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient’s parents have given consent for images and other clinical information to be reported in the journal. The patient’s parents understand that the names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.