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Year : 2020  |  Volume : 21  |  Issue : 2  |  Page : 150-152

Homozygous familial hypercholesterolemia with corneal arcus: A rare case report

Department of Pediatrics, Teerthanker Mahaveer Medical College and Research Center, Moradabad, Uttar Pradesh, India

Date of Submission19-Nov-2019
Date of Decision24-Dec-2019
Date of Acceptance30-Jan-2020
Date of Web Publication01-Apr-2020

Correspondence Address:
Bablu Kumar Gaur
Department of Pediatrics, Teerthanker Mahaveer Medical College and Research Center, Moradabad - 244 001, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpd.IJPD_112_19

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We report here a case of an 11-year-old adolescent boy who presented with asymptomatic multiple yellowish skin lesions and corneal arcus. A family history of similar complaints was present in the elder male sibling who died with underlying coronary artery disease. Laboratory findings and family history were consistent with homozygous familial hypercholesterolemia. He was started on lipid-lowering drugs and is under regular follow-up. Early diagnosis and timely initiation of treatment helped to save the affected individual and the other family members.

Keywords: Corneal arcus, hypercholesterolemia, xanthomas

How to cite this article:
Gaur BK, Maini B, Goel A. Homozygous familial hypercholesterolemia with corneal arcus: A rare case report. Indian J Paediatr Dermatol 2020;21:150-2

How to cite this URL:
Gaur BK, Maini B, Goel A. Homozygous familial hypercholesterolemia with corneal arcus: A rare case report. Indian J Paediatr Dermatol [serial online] 2020 [cited 2020 Dec 4];21:150-2. Available from: https://www.ijpd.in/text.asp?2020/21/2/150/281724

  Introduction Top

Familial hypercholesterolemia (FH) is a monogenic autosomal codominant disorder characterized by high total and low-density lipoprotein cholesterol (LDL-C), slightly low high-density lipoprotein (HDL) cholesterol, premature onset of cardiovascular disease (CVD), and tendinous xanthomas.[1] It manifests in two forms: (a) milder (heterozygous) form with a prevalence of 1 in 500 individuals, clinically manifesting in adults and (b) homozygous severe form with a prevalence of 1 in 1,000,000 individuals, clinically manifesting as early in the first decade of life.[2] Cases of homozygous FH (HoFH) inherit 2 abnormal LDL receptor genes, resulting in markedly elevated plasma cholesterol levels (ranging between 500 and 1200 mg/dL) and normal to mildly elevated triglyceride levels. Untreated HoFH patients rarely survive to adulthood as the development of coronary insufficiency eventually occurs.[3]

  Case Report Top

An 11-year-old adolescent boy born to nonconsanguineous couple presented with complaints of multiple skin-colored to slightly yellowish papules and plaques to nodular swellings over the buttocks, knees, elbow, and face for 8 years. Initially, these lesions were noticed over the knees and elbows which gradually increased in size and number. He had no significant history of any medication or trauma. Similar complaints were present in his elder brother, who had died from premature coronary artery disease at the age of 20 years. Both parents were apparently healthy and did not have any skin lesions. Examination of the child revealed multiple, subcutaneous, well-circumscribed, painless yellowish to skin-colored plaques small to large size lesions suggestive of xanthomas over both the knees [Figure 1]a, over extensor surface of both elbow [Figure 1]b, over the gluteal region [Figure 1]c, yellowish plaques over the eyelids (xanthelasma palpebrarum), and periorbital skin [Figure 1]d. Size of the lesions ranged from 2 cm to 8 cm in diameter. The ophthalmic examination revealed a circumferential white-gray deposit near the corneoscleral limbus equivalent to corneal arcus [Figure 2]. His vitals parameters and others systems were clinically normal. Blood investigations including complete blood count, liver function tests, renal function tests, and thyroid function tests were within normal limits. Ultrasonography abdomen and X-ray chest were unremarkable. Electrocardiogram and two-dimensional echocardiogram were normal. The fundus examination was normal. On investigations, fasting lipid profile of adolescent boy revealed high serum levels of total cholesterol (745 mg/dl); LDL-C (453 mg/dl), very low density LDL (28 mg/dl), triglycerides (178 mg/dl), and marginally low HDL (38 mg/dl). On the basis of Simon Broome diagnostic criteria in children aged <16 years, a diagnosis of FH was made in this case.[4] The presence of cutaneous xanthomas since childhood and elevated LDL-C in both parents suggests it to be a homozygous form.[5] He was advised low cholesterol diet and treatment with lipid-lowering drugs (Atorvastatin and Ezetimibe) was started. He was advised for regular follow-up in the pediatric and cardiology department of our hospital. At present, his lipid profile has become better but xanthomas and corneal arcus are still present. Lipid profile screening of all family members revealed high total cholesterol levels in both parents. Parents were advised cardiology workup for coronary artery disease and treatment of high lipid levels. Genetic analysis was advised but could not be done because of resource constraints.
Figure 1: (a) Xanthomas over both knees, (b) yellowish plaques over both elbows, (c) nodular lesions over both buttocks, (d) yellowish plaques on the eyelids and periorbital skin (xanthelasma palpebrarum)

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Figure 2: White-gray deposit near the corneoscleral limbus (corneal arcus)

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  Discussion Top

Homozygous familial hypercholesterolemia is a disorder of lipoprotein metabolism caused by mutations in the receptor (LDLR) gene, leading to the absence of functional receptors on the cell membrane and it causes decreased uptake of LDL into the liver cells from the blood, resulting in increased levels of LDL-C and eventually patients developed xanthomas.[6] Xanthomas are subcutaneous nodular lesions, classified as eruptive, tuberoeruptive or tuberous, tendinous, and plantar xanthomas.[7],[8] Tendinous and tuberous xanthomas are most commonly seen in FH. They are commonly found over extensor aspect of extremities. Corneal arcus in children should be regarded as an indicator of hyperlipidemia. Therefore, the presence of either xanthoma or corneal arcus should raise suspicion for hypercholesterolemia as well as the presence of premature CVD.[9] Recent studies demonstrate that patients with corneal arcus have higher cholesterol-year score and are prone to develop atherosclerosis.[10] The diagnosis of FH was made in our case based on Simon Broome Register criteria.[4] According to Simon Broome diagnostic criteria, a definitive diagnosis of FH can be made in children aged <16 years if either the total cholesterol levels is more than 260 mg/dl or the LDL-C is more than 155mg/dl plus tendinous xanthomas were present in the patient and a first or second degree relative.[4] Final diagnosis of HoFH was made on the basis of genetic or clinical criteria (LDL-C plasma concentration ≥300 mg/dL together with either: presence of cutaneous or tendon xanthomas before the age of 10 years, or the presence of elevated LDL-C levels consistent with Heterozygous FH in both parents).[5] Treatment options available for HoFH are lifestyle modification, lipid-lowering drugs such as HMG coenzyme inhibitors, ezetimibe, lipoprotein apheresis, and liver transplantation. HMG co-enzyme inhibitors now have become the mainstay of treatment and have played a major role in the reduction of cardiovascular mortality seen in HoFH. Lipoprotein apheresis is recommended for children (<8 years) as it slows the progression of atherosclerosis. Liver transplantation is also successful in decreasing LDL-C levels, but complications related to immunosuppression are common. Children should undergo regular follow-up including comprehensive cardiovascular evaluation at diagnosis, with subsequent Doppler echocardiographic evaluation of the heart and aorta annually, computed tomography coronary angiography every 5 years or more frequently if needed.[5]

Prognosis is based on percentage of receptor activity, severity of lipid level derangement, and development of coronary artery disease as well as how early the disease is detected and is given proper treatment and monitoring. Untreated HoFH patients who are LDLR-negative (<2% normal LDL receptor activity) rarely survive beyond the second decade. While HoFH patients who are LDLR-defective (2%–25% normal LDL receptor activity) have a better prognosis, almost all develop clinically significant accelerated, premature atherosclerotic CVD by the age of 30 years.[5]

This case report highlights the importance of early clinical diagnosis and appropriate regular treatment of HoFH at an early age to avoid serious cardiac complications.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Sarkany RP, Breathnach SM, Morris AA, Weismann K, Flynn PD. Metabolic and nutritional disorders. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook's Text Book of Dermatology. 8th ed. Oxford: Blackwell Publishing; 2010. p. 59.1-03.  Back to cited text no. 1
Dawoud NM, Bakry OA, Seleit I. Homozygous familial hypercholesterolemia associated with symmetric subcutaneous lipomatosis. Indian J Dermatol 2015;60:420.  Back to cited text no. 2
[PUBMED]  [Full text]  
Neal WA. Disorders of lipoprotein metabolism and transport. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson Text Book of Pediatrics. 20th ed. Philadelphia: Saunders; 2016. p. 690-704.  Back to cited text no. 3
Risk of fatal coronary heart disease in familial hypercholesterolaemia. Scientific Steering Committee on behalf of the Simon Broome Register Group. BMJ 1991;303:893-6.  Back to cited text no. 4
Cuchel M, Bruckert E, Ginsberg HN, Raal FJ, Santos RD, Hegele RA, et al. Homozygous familial hypercholesterolaemia: New insights and guidance for clinicians to improve detection and clinical management. A position paper from the consensus panel on familial hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J 2014;35:2146-57.  Back to cited text no. 5
Rader DJ, Hobbs HH. Disorders of lipoprotein metabolism. In: Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, et al., editors. Harrison's Principles of Internal Medicine. 20th ed. New York: The McGraw-Hill Companies, Inc.; 2018. p. 2532-9.  Back to cited text no. 6
Shenoy C, Shenoy MM, Rao GK. Dyslipidemia in dermatological disorders. N Am J Med Sci 2015;7:421-8.  Back to cited text no. 7
White LE. Xanthomatoses and lipoprotein disorders. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, editors. Fitzpatrick's Dermatology in General Medicine. 7th ed. United States of America: McGraw-Hill Companies, Inc.; 2008. p. 1272-81.  Back to cited text no. 8
Fernandez AB, Keyes MJ, Pencina M, D'Agostino R, O'Donnell CJ, Thompson PD. Relation of corneal arcus to cardiovascular disease (from the Framingham Heart Study data set). Am J Cardiol 2009;103:64-6.  Back to cited text no. 9
Zech LA Jr., Hoeg JM. Correlating corneal arcus with atherosclerosis in familial hypercholesterolemia. Lipids Health Dis 2008;7:7.  Back to cited text no. 10


  [Figure 1], [Figure 2]


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