The Use of Achilles Tendon Sonography to Distinguish Familial Hypercholesterolemia from Other Genetic Dyslipidemias

Abstract

Objective-Achilles tendon (AT) xanthomas, specific for familial hypercholesterolemia (FH), may be clinically undetectable. We assessed the usefulness of AT sonography in the diagnosis of FH. Methods and Results-Sonographic AT characteristics were evaluated in 127 subjects with FH (81 genetically ascertained), 84 familial combined hyperlipidemia, 79 polygenic hypercholesterolemia, and 88 normolipidemic controls. Abnormal echostructure (sonographic xanthoma) was noted only in FH. AT thickness was higher (PϽ0.001) in FH men and women compared with all of the other groups and, in FH mutation carriers but not in others, correlated positively with low-density lipoprotein cholesterol (rϭ0.345; PϽ0.001) and negatively with high-density lipoprotein cholesterol (rϭϪ0.265, Pϭ0.015). Thickness thresholds for the diagnosis of FH with specificity Ͼ80%, as were derived from receiver operating curves, were 5.3 and 5.7 mm in men Ͻ and Ͼ45 years, and 4.8 and 4.9 mm in women Ͻ and Ͼ50 years, respectively. In FH mutation carriers, sonographic findings increased the clinical diagnosis of xanthomas from 35 (43%) to 55 (68%

Achilles Tendon Ultrasonography for Diagnosis of Familial Hypercholesterolemia Among Japanese Subjects

“…Thus, it is possible that female patients with mild AT thickness may be underdiagnosed, as noted in a previous study. 11 In the present study, the median AT-T measured by US was 9.2 mm for male FH patients, and 6.2 mm for female patients ( Table 2). As there was no relationship between sex and AT-T in the linear regression analysis, we set cutoff values for both sexes to discriminate FH patients.…”

Xanthomas: Clinical and pathophysiological relations

“…Moreover, these findings can differentiate between familial hypercholesterolemia and other types of primary dyslipidemias, e.g. polygenic hypercholesterolemia, familial combined dyslipidemia 34,42 . For diagnosis of familial hypercholesterolemia, the following issues are to be considered: family history, clinical history of premature CHD, arcus senilis corneae, very high LDL cholesterol (typically above the 75 th percentile of the healthy population) on repeated measurements, and/or a causative mutation detected by molecular genetics, e.g.…”

“…Similar prevalence data (20-50%) are given by other authors for clinically diagnosed patients with familial hypercholesterolemia. Abnormal texture and thickening of Achilles tendons were demonstrated in 68% of subjects with familial hypercholesterolemia 34 . Eruptive xanthomas are pathognomic skin manifestations of severe hypertriglyceridemia (TG >11.2 mmol/L), a serious metabolic disorder with an estimated prevalence of 18 cases in 100 000 inhabitants 35 .…”

Homozygous Familial Hypercholesterolemia: Case report and Review of Literature

“…This genetic disorder is characterized by high cholesterol levels, specifically very high levels LDL and early onset of cardiovascular disease (as early as 1 st decade of life). 10,11 There is mutation in the LDL receptor gene present over chromosome 19 that encodes the LDL receptor protein, which normally removes LDL from circulation. 12,13 Also there can be mutation in apolipoprotien B (ApoB), which is the part of LDL that binds with the receptor.…”

“…21,22 Furthermore, patients may develop accumulation of cholesterol in other parts of the body leading to the development of cutaneous xanthomas of various types like xanthelasma, xanthomatendineum, and xanthoma tuberosum. 10 Management of familial hyper-cholesterolemia patients, especially homozygotes has been a challenging job. Beyond genetic counselling for patients and the families of the patients diagnosed with FH, treatment options involve decreasing serum cholesterol levels and increasing cholesterol removal.…”