Tuberous Xanthomas in Sitosterolemia

Abstract

Sitosterolemia is an autosomal recessive lipid disorder in which plasma plant sterol levels are extremely elevated and cholesterol levels are often elevated but may be normal. Clinically sitosterolemia is characterized by xanthomas, premature vascular disease, and arthritis. Adolescent boys and girls with sitosterolemia are susceptible to fatal cardiac events. Dermatologists may have a vital role in the diagnosis of this rare but serious condition because early detection and treatment are important in preventing the associated atherosclerotic heart disease. We present a 7-year-old girl with sitosterolemia and tuberous xanthomas.

Xanthomas: Clinical and pathophysiological relations

“…Hypercholesterolemia is associated with impaired lym- 2) when relapse of the disease and worsening of dyslipidemia; 3) type III HLP -needs combination of homozygocy for apoE2/E2 (with autosomal recessive heritability) and other hyperlipidemia-forming factor (familiar DLP) or the presence of secondary DLP (decompensated DM, hypothyreosis, obesity, alcohol intake, pharmacologic dosage of estrogens). 4) onset of severe HTG (type V HLP with high VLDL and presence of chylomicrons) 5) PHC is caused by combination of exogenous and genetic factors (mutations/polymorphisms in apoE4, CETP, hepatic lipase, LPL, PCSK9, ABCG5/G8, LCAT, CYP7A1); 6) FCH -it is supposed that the polymorphisms of apoB-100, LPL, apoE, cluster of apoC-III/apoA-I/apoA-IV take part in the pathophysiology of the disease; the defects/polymorphisms of apoC-II and receptor for acylation stimulating protein (ASP) are also possible. 7) FH3 -some patients have mutations in the PCSK9 gene encoding neural apoptosis regulated convertase 2 (NARC-1) which enhances the degradation of LDL-receptors.…”

“…The diagnosis can be confirmed by molecular genetic examination of ABCG5/ABCG8 transporters (ref. 5,45 ). Laboratory examination in patients with cerebrotendinous xanthogranulomatosis shows increased plasma concentrations of cholestanol (about six times) and high urinary excretion of bile alcohols.…”

“…Xanthomas can also call attention to the presence of some uncommon conditions, such as cerebrotendinous xanthomatosis caused by mutations in the sterol 27-hydroxylase gene (CYP27A) which induce a 27-hydroxylase deficiency, and familial β-sitosterolemia (phytosterolemia) with mutations in the genes encoding the specific sterol transporters ABCG5 and ABCG8 (ref. 5,6 ). The development of xanthomas can signalise an elevated risk for serious metabolic and cardiovascular diseases, as well as for lymphoproliferative malignancies.…”

Liver disease associated with canalicular transport defects: Current and future therapies

“…This disease is characterized by an increased retention of sitosterols by the intestine and a failure to secrete sterols into bile, resulting in high plasma sitosterol levels and accumulation of sterols in peripheral tissues and blood [84][85][86][87]. Patients consequently present with tendon xanthomas, arthralgias and premature coronary artery disease, despite relatively low plasma levels of cholesterol [88][89][90] (Table 1). Sporadically, haemolytic abnormalities are mentioned [91].…”

“…However, extensive experiments are available for sitosterolaemia in which cholestyramine in combination with a diet low in cholesterol reduced the serum levels of plant sterols with improvement of clinical symptoms, such as reduction of xanthomas [88,93,[128][129][130][131][132] (Table 2C). Chronic cholestyramine treatment may cause constipation, but no other serious complications have been found.…”