Familial Hypercholesterolemia: Report of a Family


Dr Suprabha Shukla, Dr Dillip Kumar Das, Dr Narayan Prasad Modi    23 January 2018


Hypercholesterolemia, corneal arcus, xanthomas

Familial hypercholesterolemia (FH) is caused by mutations in the low-density lipoprotein (LDL) receptor, which prevent its synthesis, reduce its appearance on the cell surface, or impair its ability to bind and internalize LDL. Elevated LDL cholesterol levels lead to the major complication of this condition: Premature atherosclerotic cardiovascular disease. Homozygous FH is a rare variant, occurring with a frequency of 1:1,000,000.1 We present a family of homozygote manifesting with corneal arcus and multiple xanthomas.

Case report

We are reporting two male siblings of age 8 years and 6 years, born out of consanguineous marriage with history of xanthomatous lesions for 5 and 3 years, respectively. Anthropometry was normal in both the cases.

Physical examination showed presence of subcutaneous yellow nodules and plaques over the knuckles, elbows, knee, buttock and umbilicus of size up to 5 cm in size and in some regions tended to coalesce, suggestive of xanthoma and having both tendinous and tuberous xanthomas. One of the siblings (elder) had corneal arcus without vision abnormality. Systemic examination was normal in both siblings. Mother had also multiple tendinous xanthomas and corneal arcus. Father died at the age of 34 years from sudden cardiac arrest. Investigation of the both siblings and mother were done to arrive at a diagnosis. Complete blood count, liver, renal and thyroid function tests were normal. Chest X-ray, ECG, echocardiography of all three were normal. Lipid profile of the siblings and mother were done suspecting FH (Table 1). Biopsy of the skin lesion was done; this was suggestive of xanthoma.

With these presentations, diagnosis of familial homozygous hypercholesterolemia was considered as mother and siblings had corneal arcus and xanthoma and had very high LDL and total cholesterol with normal triglyceride level.

But, due to unavailability of LDL receptor activity test, it could not be done. Both the siblings were treated with statin group of drugs (simvastatin 10 mg daily) and fat restricted diet. Now the family is under follow-up and the skin lesions flattening to some extent.


Familial hypercholesterolemia is inherited as an autosomal dominant disorder. The gene for LDL receptor found in chromosome 19. It may be heterozygous or homozygous variety.2

The prevalence of heterozygotes is 1 in 500 in populations. Although plasma cholesterol level is increased 2- to 3-fold since birth, but they became symptomatic in 3rd-6th decade of life with tendon xanthoma and cardiovascular complications. Response to treatment in these patients is good.2

Homozygous FH is clinically characterized by cutaneous xanthomas, enlarged achilles tendons, atherosclerosis and corneal arcus, usually developing from early childhood.

Tendinous xanthoma is asymptomatic slowly enlarging subcutaneous nodules attached to tendons, ligaments, fascia and periosteum with normal overlying skin. Extensor tendons of hands, feet and achilles tendon are involved more frequently. They are often found in association with severe hypercholesterolemia and elevated LDL level (Fredrickson type 2) and occasionally in hypercholesterolemia associated with prolonged cholestasis.3,4

Some patients with homozygous FH do not have cutaneous xanthomas but acquire tuberous or tendon xanthomas on the elbows, knees or achilles tendons as older children or adolescents.5 The absence of xanthomas in children does not exclude the diagnosis. Arcus cornea may be present to some degree. Total cholesterol levels are usually >500 mg/dL and can be as high as 1,200 mg/dL. The major complication of homozygous FH is accelerated atherosclerosis, which can result in clinical sequelae even in childhood. Homozygous FH children often have symptoms of vascular disease before puberty, but symptoms can be atypical or go unreported; sudden death is common.6

A child with relatively normal triglycerides and a total cholesterol level >500 mg/dL  with or without cutaneous or tendon xanthomas, should be suspected of having homozygous FH. Parents and other relatives should be screened for hypercholesterolemia. Obstructive liver disease and nephrotic syndrome should be excluded in each case. The diagnosis is mainly made on clinical grounds but can be confirmed in specialized centers by obtaining a skin biopsy specimen and performing an assay of the LDL receptor activity on the skin fibroblasts.6 Early combination therapy with LDL apheresis, statins and cholesterol absorption inhibitors are advised in children with homozygous FH at the highest risk. Our patients were managed with statin group of drug. These patients need regular follow-up and evaluation for underlying cardiac complication.


  1. Rader DJ, Cohen J, Hobbs HH. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J Clin Invest 2003;111(12):1795-803.
  2. van Aalst-Cohen ES, Jansen AC, de Jongh S, de Sauvage Nolting PR, Kastelein JJ. Clinical, diagnostic, and therapeutic aspects of familial hypercholesterolemia. Semin Vasc Med 2004;4(1):31-41.
  3. Pandhi D, Grover C, Reddy BS. Type IIa hyperlipoproteinemia manifesting with different types of cutaneous xanthomas. Indian Pediatr 2001;38(5): 550-3.
  4. Somwanshi PR, Agarwal NS. Homozygous familial hypercholesterolemia (le). Indian J Dermatol Venereol Leprol 2000;66(6):331-2.
  5. Zech LA Jr, Hoeg JM. Correlating corneal arcus with atherosclerosis in familial hypercholesterolemia. Lipids Health Dis 2008;7:7.
  6. William A. Neal. Nelson Textbook of Pediatrics. 19th edition, Elsevier 2011:p.473-4.

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