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Year : 2015  |  Volume : 60  |  Issue : 4  |  Page : 420
Homozygous familial hypercholesterolemia associated with symmetric subcutaneous lipomatosis

Department of Dermatology, Andrology and STDs, Menoufiya University, Egypt

Date of Web Publication10-Jul-2015

Correspondence Address:
Dr. Noha Mohammed Dawoud
Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufiya University, Shebin Elkoom - 32817
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.160519

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Homozygous familial hypercholesterolemia is an autosomal dominant disorder of lipid metabolism, characterized by reduced clearance of low-density lipoprotein-cholesterol and a high risk of rapid development of cardiovascular diseases. Its incidence is relatively rare and estimated to be one in one million in general populations. Here, we report homozygous familial hypercholesterolemia in two Egyptian young siblings, presented with cutaneous, tendinous xanthomas, and corneal arcus. One of them has symmetric subcutaneous lipomatosis, which has not been reported before in association with familial hypercholesterolemia.

Keywords: Familial hypercholesterolemia, subcutaneous lipomatosis, xanthomas

How to cite this article:
Dawoud NM, Bakry OA, Seleit I. Homozygous familial hypercholesterolemia associated with symmetric subcutaneous lipomatosis. Indian J Dermatol 2015;60:420

How to cite this URL:
Dawoud NM, Bakry OA, Seleit I. Homozygous familial hypercholesterolemia associated with symmetric subcutaneous lipomatosis. Indian J Dermatol [serial online] 2015 [cited 2022 Sep 29];60:420. Available from:

What was known?

  1. Familial hypercholesterolemia (FH) is an autosomal dominant disorder resulting in elevated plasma low-density lipoprotein-cholesterol (LDL-C).
  2. Clinically, homozygous FH is presented by cutaneous, tendon xanthomas, arcus cornealis, and generalized atherosclerosis developing during childhood. However, hypercholesterolemia is usually the only clinical finding in children with heterozygous FH in their first decade of life.

   Introduction Top

Familial hypercholesterolemia (FH) is an inherited autosomal dominant disorder of lipid metabolism. It is caused by a defect in chromosome 19 and characterized by raised levels of low-density lipoprotein-cholesterol (LDL-C) ("bad cholesterol") that is passed down through families. The condition begins at birth and can cause heart attacks at an early age. [1]

Clinically, FH is characterized by deposits of cholesterol in the vascular wall, causing atheromas, and extravascularly in the form of xanthomas, especially in the skin and tendons of patients with severe hyperlipidemia. [2] Here, we present two young Egyptian siblings with FH.

   Case Report Top

Two young sisters of age 6 and 4 years, born to a consanguineous marriage, presented to our dermatology clinic complaining of scattered, painless, and yellowish papules and nodules since birth progressively increasing in number and size.

On examination, both children had intertriginous yellowish xanthomatous plaque in the gluteal cleft since birth (1 × 2 cm) [Figure 1]a] and scattered yellowish xanthomas on both knees [Figure 1]b and [Figure 2]c] and elbows [Figure 1]c]. In addition, the younger sister had yellowish streaks of plane xanthoma on the side and back of the neck [Figure 2]a], periumbilical xanthoma [Figure 2]b] and two subcutaneous soft swellings below the knees [Figure 2]c]. Ophthalmologic examination revealed lipid deposition in the cornea of both patients (arcus juvenilis) [Figure 1]d and [Figure 2]d]. Orthopedic examination also revealed thickened Achilles tendons of both patients.
Figure 1: Older patient: Multiple xanthomas; intergluteal cleft (a) knees (b) elbows (c) and arcus juvenilis of corneae (d). Inset: Foamy xanthoma cells occupying the dermis (H and E, ¡¿200)

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Figure 2: Younger sister: Multiple xanthomas; sides and back of neck (a) periumbilical (b) knees with subcutaneous lipomatosis (c) and arcus juvenilis of corneae (d)

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Lipid profile was done for patients, mother, and father, and it revealed elevated total and LDL-C levels with normal triglycerides and high-density lipoprotein-cholesterol (HDL-C) levels [Table 1]. Blood sugar level, thyroid function tests, complete blood count, urine analysis, and liver and renal function tests were all normal, excluding secondary hypercholesterolemia. Hematoxylin and eosin-stained sections of the biopsied lesions revealed sheets and groups of foamy xanthoma cells with central nuclei occupying the whole dermis [Figure 1] Inset].
Table 1: Lipid profile of patient, her younger sister, father, and mother

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Echocardiography of both sisters and their parents revealed no abnormality. Ultrasound for Tendo-Achilles showed fusiform thickening with intrasubstance hypoechoic areas compatible with xanthoma. Ultrasound for the subcutaneous knee swellings revealed bilateral and symmetrical subcutaneous lipomatosis on the extensor aspect of both knees. Therefore, based on clinical, laboratory, and radiological findings, the diagnosis of homozygous FH was reached.

The whole family was advised to consume a diet low in cholesterol and saturated fat and rich in unsaturated fat in addition to lipid lowering drugs. Atorvastatin was prescribed for both patients (10 mg daily) and their parents (20 mg daily). After one month of treatment, the cholesterol level was reduced to 542 mg/dl in the older patient and to 500 mg/dl in the younger patient. All patients and their parents are still under treatment and follow-up.

   Discussion Top

FH is clinically diagnosed by confirming the family history and characteristic findings such as cutaneous and tendon xanthomas. Cutaneous xanthomas may initially present in the intergluteal cleft or interdigital spaces on the dorsal surface of the hands and feet. Planar surfaces over the elbows and knees are the other common sites of appearance of xanthomas. [2] Of the affected individuals with FH, 75% complain of tendon xanthomas, usually located in the Achilles or extensor tendons of the hands. Achilles tendon xanthomas can be detected by physical examination and better detected by ultrasonography. Therefore, arthritis and tendinitis may attract attention to the diagnosis of patients with FH. [3]

Xanthomas develop because of lipid leakage from the vasculature into the surrounding tissues, where macrophages subsequently phagocytose these lipids. Because cholesterol is not degraded, it accumulates within these cells, creating foamy macrophages. The extracellular cholesterol crystallizes into the clefts, inducing an inflammatory reaction with giant cells and resultant fibrosis. [4]

FH has two forms: Heterozygous and homozygous. Heterozygous FH is more common, with a reported prevalence of 1/500 and plasma LDL-C in the range of 297-425 mg/dl. Homozygous FH is rare, with a prevalence of 1/1,000,000 with plasma LDL-C of 444-1089 mg/dl. [5]

Our patients-the two young sisters-were diagnosed as having homozygous FH, since their serum cholesterol level was more than 600 mg/dl; moreover, their parents have raised serum cholesterol level more than 200 mg/dl. Both cases had cutaneous intertriginous and tuberous xanthomas since birth, tendinous xanthomas with thickened Achilles tendon, and arcus juvenilis of the cornea in the first decade of life, but fortunately, without cardiovascular complications yet. This goes with other authors who set the diagnostic criteria of homozygous FH [Table 2].
Table 2: Diagnostic criteria for homozygous FH from the literature

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Effective FH screening by cholesterol testing should be done for all members of the extended family. The treatment of FH consists of a diet low in total and saturated fats with a combined drug therapy. [9] Effective drug combinations include low doses of bile acid sequestrants together with HMG-CoA reductase inhibitors or niacin or all these agents combined. [2] A new third-generation statin, rosuvastatin demonstrated a significantly greater reduction in LDL-C as well as significantly greater increase in HDL-C compared to atorvastatin. [9] So, aggressive treatment including diet control, lipid lowering drugs, exercise, and control of risk factors will help reduce the morbidity and mortality associated with this disease. Follow-up is mandatory for monitoring treatment and early detection of cardiovascular complications and prompt treatment.

To the best of our knowledge, the association between FH and symmetrical subcutaneous lipomatosis was not reported before, and we present our case as the first report of this association. Whether there is a genetic association between both conditions or it is an accidental combination, it requires further research. However, Rubinstein et al. [10] reported a family with familial combined hyperlipidemia wherein the affected members had nonsymmetric subcutaneous lipomatosis, and suggested the existence of a genetic linkage between the two characteristics. Moreover, they found a correlation between the degree of hyperlipidemia and the amount of these subcutaneous lipomas. [10]

   References Top

Genest J, Libby P. Lipoprotein disorders and cardiovascular disease. In: Bonow RO, Mann DL, Zipes DP, Libby P, editors. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. Philadelphia, PA: Saunders Elsevier; 2011; Chap 47.  Back to cited text no. 1
Ginsberg HN, Goldberg IJ. Disorders of lipoprotein metabolism. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors. Harrison's Principles of Internal Medicine. New York: McGraw-Hill; 2001.Chap 356.  Back to cited text no. 2
Tsouli SG, Kiortsis DN, Argyropoulou MI, Mikhailidis DP, Elisaf MS. Pathogenesis, detection and treatment of Achilles tendon xanthomas. Eur J Clin Invest 2005;35:236-44.  Back to cited text no. 3
Jackler RK, Brackmann DE. Xanthoma of the temporal bone and skull base. Am J Otol 1987;8:111-5.  Back to cited text no. 4
Marks D, Thorogood M, Neil HA, Humphries SE. A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis 2003;168:1-14.  Back to cited text no. 5
Haitas B, Baker SG, Meyer TE, Joffe BI, Seftel HC. Natural history and cardiac manifestations of homozygous familial hypercholesterolaemia. Q J Med 1990;76:731-40.  Back to cited text no. 6
Goldstein JL, Hobbs HH, Brown MS. Familial hypercholesterolemia. In: Scriver CR, Ellenson LH, Ellis NA, et al., editors. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill Medical Publishing Division; 2001; 2863-913.  Back to cited text no. 7
Santos RD, Miname MH, Martinez LR, Rochitte CE, Chacra AP, Nakandakare ER, et al. Non-invasive detection of aortic and coronary atherosclerosis in homozygous familial hypercholesterolemia by 64 slice multi-detector row computed tomography angiography. Atherosclerosis 2008;197:910-5.  Back to cited text no. 8
Davidson MH. Rosuvastatin: Ahighly efficacious statin for the treatment of dyslipidaemia. Expert OpinInvestig Drugs 2002;11:125-41.  Back to cited text no. 9
Rubinstein A, Goor Y, Gazit E, Cabili S. Non-symmetric subcutaneous lipomatosis associated with familial combined hyperlipidaemia. Br J Dermatol 1989;120:689-94.  Back to cited text no. 10

What is new?

  1. We present our case as the first report of the association between homozygous FH and subcutaneous lipomas, which are interestingly symmetrically distributed.
  2. Is there a relationship between the amount of these lipomas and the level of hyperlipidemia? Is there a genetic linkage between those entities or an accidental association? The answers to these questions require further research.


  [Figure 1], [Figure 2]

  [Table 1], [Table 2]

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