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Year : 2018  |  Volume : 19  |  Issue : 3  |  Page : 245-247

Homozygous familial hypercholesterolemia: A rare case report

Department of Dermatology, Venereology and Leprosy, MNR Medical College and Hospital, Sangareddy, Telangana, India

Date of Web Publication28-Jun-2018

Correspondence Address:
Dr. Geeta Kiran Arakkal
Department of Dermatology, Venereology and Leprosy, MNR Medical College and Hospital, Sangareddy - 502 294, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpd.IJPD_47_17

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A 9-year-old male child presented with asymptomatic skin-colored-to-yellowish nodules over both the buttocks, feet, and over the right Achilles' tendon for 4 years. There was a history of similar complaints in elder sibling and also a history of premature sudden cardiac death in father. Biopsy from the lesions was suggestive of xanthoma. Fasting lipid profile was consistent with the pattern of Type IIa hyperlipoproteinemia. The child was further worked up for systemic involvement which was normal. He was started on rosuvastatin and fenofibrate and is under regular follow-up. The timely diagnosis of familial hypercholesterolemia, especially the homozygous variant, is important for early intervention and prevention of complications.

Keywords: Familial, lipid profile, xanthomas

How to cite this article:
Malkud S, Varala S, Arakkal GK, Badabagni P. Homozygous familial hypercholesterolemia: A rare case report. Indian J Paediatr Dermatol 2018;19:245-7

How to cite this URL:
Malkud S, Varala S, Arakkal GK, Badabagni P. Homozygous familial hypercholesterolemia: A rare case report. Indian J Paediatr Dermatol [serial online] 2018 [cited 2021 Jan 21];19:245-7. Available from: https://www.ijpd.in/text.asp?2018/19/3/245/211818

  Introduction Top

Xanthomas are subcutaneous lipid depositions usually caused by derangement of lipoprotein metabolism.[1] They are considered to be the marker of hyperlipoproteinemia.[2] Xanthomas in children and adolescents are more suspicious of severe form of hyperlipidemias.[3] Here, we report a case of tuberous and tendinous xanthomas in a 9-year-old child with the lipid profile pattern consistent with Type IIa hyperlipoproteinemia.

  Case Report Top

A 9-year-old male child born to second-degree consanguineous couple presented with multiple asymptomatic swellings over the buttocks and feet for 4 years. They were insidious in onset and gradually progressive. Initially, lesions were noticed over the buttocks which gradually increased in size and number while progressing to the feet. The patient was otherwise healthy with no systemic complaints. A history of similar complaints was present in the elder sibling. The patient's father died of myocardial infarction at the age of 42 years. Cutaneous examination revealed multiple, well-circumscribed, nontender, mobile, yellowish-to-skin-colored nodules over both the buttocks [Figure 1], medial aspect of base of both great toes, and lateral aspect of the left fifth toe [Figure 2]. Size of the nodules was ranging from 1 cm to 5 cm in diameter with soft to firm consistency. A solitary firm nodule measuring 2 cm × 1 cm was seen over the lower part of the right Achilles' tendon [Figure 3]. Skin over elbows, knees, palms, and soles was normal. Investigations including complete blood count, liver function tests, renal function tests, thyroid function tests, ultrasonography of abdomen, electrocardiogram, and chest X-ray were within normal limits. His fasting lipid profile showed increased levels of total cholesterol (536 mg/dl) and low-density lipoprotein (LDL) (472 mg/dl), with normal very LDL (VLDL) (21 mg/dl), triglycerides (105 mg/dl), and high-density lipoprotein (HDL) (43 mg/dl) levels. Lipoprotein(a) (Lp[a]) quantification was performed and levels were 47.80 mg/dl. Slit lamp and fundus examination of the eyes were normal. Excision biopsy of small nodule over gluteal region was done and sent for histopathological examination. Hematoxylin and eosin (H and E) stain showed plenty of foamy macrophages with areas of cholesterol clefts in the collagen bundles [Figure 4]. Based on history, clinical features, and investigation findings, a diagnosis of homozygous familial hypercholesterolemia (FH) with tuberous and tendinous xanthoma was made. Lipid profile screening of all family members was advised as this condition is familial. Dietary advice regarding strict control of fat was given. The patient was started on lipid-lowering drugs – rosuvastatin 5 mg/day and fenofibrate 72.5 mg/day – and is under regular follow-up.
Figure 1: Multiple yellowish nodules over gluteal region

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Figure 2: Nodules at the base of both great toes and over the left little toe

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Figure 3: Solitary nodule over lower part of the right Achilles' tendon

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Figure 4: Histopathological section (H and E stain) showing (a) cholesterol clefts (×10), (b) foamy macrophages (×40)

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  Discussion Top

Xanthomas are cutaneous lesions seen as a result of altered lipoprotein metabolism. It may arise even without any intrinsic metabolic defects.[4] Xanthomas are benign plaques or nodules consisting of macrophages laden with cholesterol and cholesterol esters (foam cells).[5]

Frederickson classified hyperlipoproteinemias into five types based on electrophoretic banding of plasma lipoprotein fractions.[6] Type I and Type IIa are familial forms and usually seen in children. Type IIa, also called FH, is an inherited autosomal dominant condition which has two forms, i.e. heterozygous and homozygous. Heterozygous FH is more common, with a prevalence of 1 in 500 whereas homozygous FH is rare, with a reported prevalence of 1 in 1,000,000.[7] Symptoms developing early in life with very high cholesterol levels are usually seen in homozygotes which is also the scenario in our case while heterozygotes develop symptoms in third to sixth decades of life. A definitive diagnosis of FH was made in our case based on Simon Broome Register criteria for diagnosing FH.[8] Defective functioning of LDL receptor leading to accumulation of LDL was found to be the underlying abnormality of FH. Clinically, FH presents with tuberous, tendinous, tuberoeruptive, and planar xanthomas.[9] The principal cutaneous manifestation of FH is the presence of tendon xanthomas seen frequently over the extensor tendons, especially the Achilles' tendon and those over knuckles, and is often helpful in establishing the diagnosis. Though they are cardinal cutaneous manifestations, they are not invariably present, especially if treatments to reduce the LDL cholesterol were initiated at a sufficiently early age.[10]

Tuberous xanthomas present as firm, painless, yellow-red nodules usually seen over the extensor areas of the limbs, buttocks, and pressure areas.[11] Fibrous tissue and cholesterol content make xanthomas nodule feel hard which may also get inflamed. The condition is characterized by raised total and LDL cholesterol, slightly low HDL cholesterol, and normal triglyceride levels.[4]

Histopathology of tuberous xanthoma is characteristic and similar to tendon xanthomas with large aggregates of foam cells, which are macrophages containing lipid, with areas of cholesterol clefts in the dermis. Touton giant cells or other inflammatory cells are usually not seen.[12]

Treatment options include lifestyle modification with dietary changes and medications. Statins which inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase enzyme in cholesterol synthesis are used in reducing the cholesterol levels.[13] Other lipid-lowering drugs that can be combined with statins are bile acid sequestrants, ezetimibe, niacin, fibrates, and probucol.[10],[14] Tendon xanthomas may respond to lipid-lowering drugs while tuberous xanthomas which are large might require surgical excision.[10]

There is a striking preponderance of coronary artery disease in patients with FH leading to premature onset of cardiovascular disease (CVD) and sudden cardiac death. Raised serum total and LDL cholesterol and associated endothelial dysfunction are implicated as the cause.[15] Elevated Lp(a) is also an independent CVD risk factor in patients with FH.[16]

When xanthomas occur in children and adolescents, it indicates a more severe form of hyperlipidemia. Hence, early diagnosis and treatment is important in preventing complications.

  Conclusion Top

The diagnosis of xanthomas, especially in younger age group, is important for the fact that they are indicators of development of premature coronary artery disease. Early diagnosis and treatment and screening of the family members help in decreasing the risk of such complications. This case particularly being a homozygous variant is presented for its rarity.

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  References Top

Shenoy C, Shenoy MM, Rao GK. Dyslipidemia in dermatological disorders. N Am J Med Sci 2015;7:421-8.  Back to cited text no. 1
Lugo-Somolinos A, Sánchez JE. Xanthomas: A marker for hyperlipidemias. Bol Asoc Med P R 2003;95:12-6.  Back to cited text no. 2
Mohan KK, Kumar KD, Ramachandra BV. Tuberous xanthomas in type IIA hyperlipoproteinemia. Indian J Dermatol Venereol Leprol 2002;68:105-6.  Back to cited text no. 3
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Pathania V, Yadav A. A case of familial hypercholesterolaemia type IIa presenting with tuberous xanthomas. Med J Armed Forces India 2015;71 Suppl 1:S254-6.  Back to cited text no. 4
Bansal M, Manchanda K, Pandey SS. Familial type IIa hyperlipoproteinemia presenting with different types of xanthomas. Indian J Paediatr Dermatol 2014;15:39-41.  Back to cited text no. 5
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Fredrickson DS, Levy RI, Lees RS. Fat transport in lipoproteins – An integrated approach to mechanisms and disorders. N Engl J Med 1967;276:215-25.  Back to cited text no. 6
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. 7
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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. 8
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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. 59.1-59.103  Back to cited text no. 10
Babu R, Venkataram A, Santhosh S, Shivaswamy S. Giant tuberous xanthomas in a case of type IIa hypercholesterolemia. J Cutan Aesthet Surg 2012;5:204-6.  Back to cited text no. 11
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Weedon D. Cutaneous infiltrates-non-lymphoid. In: Weedon D, editor. Weedon's Skin Pathology. 3rd ed. Philadelphia: Elsevier Limited; 2010. p. 961-4.  Back to cited text no. 12
Pahan K. Lipid-lowering drugs. Cell Mol Life Sci 2006;63:1165-78.  Back to cited text no. 13
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. Turk Kardiyol Dern Ars 2015;43 Suppl 1:1-14.  Back to cited text no. 14
Austin MA, Hutter CM, Zimmern RL, Humphries SE. Familial hypercholesterolemia and coronary heart disease: A HuGE association review. Am J Epidemiol 2004;160:421-9.  Back to cited text no. 15
Nordestgaard BG, Chapman MJ, Ray K, Borén J, Andreotti F, Watts GF, et al. Lipoprotein(a) as a cardiovascular risk factor: Current status. Eur Heart J 2010;31:2844-53.  Back to cited text no. 16


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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