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Case Report Homozygous Familial Hypercholesterolemia with Valvulopathy Departments of 1Cardiology, 2 Internal Medicine, 3 Neurology, Baby Memorial Hospital, Calicut, Kerala, India Received: June, 2018. Accepted: July, 2018.
Abstract
Ashokan Nambiar1, DM; Robin George Manappallil2, MD; V G Pradeep Kumar3, DM; Avinash Sarpamale2, MBBS Familial hypercholesterolemia (FH) is an autosomal codominant genetic disorder of lipid metabolism. The occurrence of its homozygous form is rare. This is a case of a young girl who presented with syncope and was found to have multiple tuberous xanthomas and valvulopathy, along with deranged lipid profile, suggestive of homozygous FH. Keywords: Aortic regurgitation, aortic stenosis, ezetimibe, hypercholesterolemia, statin
Introduction
F
amilial hypercholesterolemia (FH) is an autosomal codominant genetic disorder characterized by an elevated level of low‑density lipoprotein (LDL) cholesterol (in the absence of hypertriglyceridemia), cutaneous xanthomas, and premature coronary atherosclerosis. The condition is uncommon, with an incidence of 0.2% in general population. There are two forms of FH: heterozygous FH (HeFH) and homozygous FH (HoFH). HeFH is more common with a prevalence of 1 per 250–500 individuals, while HoFH is rare with a prevalence of only 1 in 1,000,000 population.[1,2] These patients are at high risk of developing coronary artery disease (CAD) and sudden death, requiring prompt recognition and treatment.[3] Screening of first‑degree relatives also plays an important role in this condition.
Case Report A 19‑year‑old girl presented with complaints of recurrent syncope for the past 1 year. She also had New York Heart Association Class II dyspnea and angina since 2 years. She was born of consanguineous marriage (parents were first cousins) [Figure 1]. She had normal developmental milestones. On examination, she had a low volume pulse of 98/minute and blood pressure of 110/60 mmHg. Multiple tuberous xanthomas were present over her elbows [Figure 2] and gluteal region, nodular lesions over her knuckles and intertriginous xanthomas in the web spaces of her hands [Figure 3], xanthomas over her feet [Figure 4], and xanthelasma without arcus cornealis [Figure 5]. Her cardiovascular examination revealed an ejection systolic murmur in the aortic region with radiation to the carotids and a pansystolic murmur in the mitral area conducted to the axilla. Electrocardiography had ST depression in leads II, III, aVF, and V4–6 [Figure 6]. Echocardiography showed severe valvular calcific stenosis of tricuspid aortic valve, moderate aortic regurgitation, and moderate mitral regurgitation (partly valvular and partly papillary) with the left ventricular ejection fraction of 65%. There was no regional Access this article online Quick Response Code: Website: www.jcpconline.org
DOI: 10.4103/JCPC.JCPC_26_18
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wall motion abnormality. Severe concentric left ventricular hypertrophy was present. Tricuspid and pulmonary valves were normal with no pulmonary artery hypertension. The aorta was also normal. Her lipid profile was grossly deranged with LDL 848 mg/dL, high‑density lipoprotein (HDL) 22 mg/ dL, and triglycerides 50 mg/dL. HbA1c, TSH, and renal and liver functions were normal. Urine examination did not show proteinuria. Ultrasound abdomen showed Grade 1 fatty liver. Her parents and sister also had high LDL levels but no skin or cardiac lesions. Her father had arcus cornealis. Her paternal grandmother and maternal grandfather (who happen to be siblings) died of myocardial infarction at the age of 45 and 50 years, respectively. On the basis of her history, clinical findings, and lipid profile reports, the diagnosis of HoFH with valvulopathy was made. She was started on rosuvastatin 20 mg once daily (as she was not tolerating higher doses) and ezetimibe 10 mg once daily, along with dietary restrictions. She was advised aortic and mitral valve replacement. In view of the high incidence of CAD in HoFH and the need for valve replacement, the patient was also advised coronary angiogram, but she and her parents were not willing for it. Genetic studies were not done due to financial restraints and lack of availability. The probable need for LDL apheresis and liver transplantation was also explained. However, after discharge, she was lost for follow‑up.
Discussion FH is caused by the loss‑of‑function mutations in the LDL‑receptor genes. As a result, there is reduced clearance of LDL from the circulation by the liver. HoFH individuals have a much higher levels of LDL compared to HeFH.[2] Address for correspondence: Dr. Robin George Manappallil, MD, Department of Internal Medicine, Baby Memorial Hospital, Calicut ‑ 673 004, Kerala, India. E‑mail:
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How to cite this article: Nambiar A, Manappallil RG, Pradeep Kumar VG, Sarpamale A. Homozygous familial hypercholesterolemia with valvulopathy. J Clin Prev Cardiol 2019;8:34-7.
© 2019 Journal of Clinical and Preventive Cardiology | Published by Wolters Kluwer ‑ Medknow
[Downloaded free from http://www.jcpconline.org on Monday, February 11, 2019, IP: 82.178.182.113] Nambiar, et al.: Homozygous familial hypercholesterolemia
Figure 1: Pedigree chart
Figure 2: Tuberous xanthoma over the elbow
Figure 3: Intertriginous xanthomas in the web spaces of the hands
Figure 4: Xanthomas over the feet
in the range of 200–400 mg/dL with normal triglycerides. The onset of disease is from birth, and recognition is based on hypercholesterolemia on routine screening with the development of xanthomas or cardiovascular conditions. These patients have a strong family history of premature heart disease. Physical examination reveals corneal arcus and tendon xanthomas mainly involving the dorsum of hands and Achilles tendon.[2]
Figure 5: Xanthelasma
HoFH is caused by the mutation of two alleles of LDL receptor. They can be classified as receptor negative (i.e., those with no LDL‑receptor activity) and receptor defective (i.e., those with markedly reduced but detectable receptor activity). These patients have high LDL levels, ranging from 400 to more than 1000 mg/dL, with normal triglycerides. The presentation is usually in childhood with cutaneous xanthomas on the hands, wrists, elbows, knees, heels, and buttocks.[2] The presence of intertriginous xanthomas is a marker of HoFH.[3] There is a high risk of atherosclerotic cardiovascular disease in childhood or early adulthood.[4] Sudden death is uncommon. Untreated patients rarely survive beyond the second decade.[2] HeFH, on the other hand, is caused by the inheritance of one LDL‑receptor mutant allele. The high LDL levels are usually
There are several diagnostic criteria for the diagnosis of FH. Of these, the commonly used Dutch Lipid Clinic Network (DLCN) criterion is shown below [Table 1]. A score of more than 8 is definite FH, while scores of 6–8, 3–5, and
