Prominent Tendon Xanthomas and Abdominal Aortic Aneurysm Associated with Cerebrotendinous Xanthomatosis Identified Using Whole Exome Sequencing

Tada, Hayato; Inaba, Syota; Pozharitckaia, Daria; Kawashiri, Masa‐aki

doi:10.2169/internalmedicine.9687-17

Cited by 13 publications

(9 citation statements)

References 11 publications

(10 reference statements)

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“…Her clinical workup consisted of biochemical testing for CTX which revealed an elevation of the cholestanol precursor 7α,12α‐dihydrocholest‐4‐en3‐one (Table 1) and molecular analysis of the CYP27A1 gene that revealed two pathogenic variants: c.410G > A (p.Arg137Gln) and c.1183C > T (p.Arg395Cys). Both of these variants have been reported previously (Table 2), including some cases with corresponding biochemical data 12‐19 . This patient's imaging has been described previously 20 and is consistent with rare previous reports of spinal xanthomatosis occurring both with 4 and without brain lesions 21 .…”

Section: Case Reportsupporting

confidence: 90%

Familial variability of cerebrotendinous xanthomatosis lacking typical biochemical findings

et al. 2021

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Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of bile acid synthesis caused by pathogenic variants in the CYP27A1 gene encoding the mitochondrial enzyme sterol 27‐hydroxylase. Patients with CTX can present with a wide range of symptoms, but most often have evidence of tendon xanthomas along with possible cataracts, atherosclerosis, or neurological dysfunction. Regardless of clinical phenotype, CTX patients typically exhibit levels of cholestanol and bile acid precursors in the circulation that are many fold increased over normal control concentrations. Here we report two siblings, one with the rare spinal xanthomatosis phenotype and the other with a very mild form of CTX manifesting as minor tendon xanthomatosis and gastrointestinal complaints who both carry compound heterozygous variants in CYP27A1: NM_000784.3: c.410G > A (p.Arg137Gln) and c.1183C > T (p.Arg395Cys). However, biochemical analysis of these patients revealed normal levels of serum cholestanol and relatively mild elevations of the bile acid precursors 7α‐hydroxy‐4‐cholesten‐3‐one and 7α,12α‐dihydroxy‐4‐cholesten‐3‐one. The atypical biochemical presentation of these cases represents a diagnostic challenge for a disorder once thought to have a sensitive biomarker in cholestanol and highlight the need for thorough investigation of patients with symptomatology consistent with CTX that includes bile acid precursor biochemical testing and molecular analysis.

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Section: Case Reportsupporting

confidence: 90%

Familial variability of cerebrotendinous xanthomatosis lacking typical biochemical findings

et al. 2021

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“…It is not easy to make a differential clinical diagnosis of sitosterolemia (Fig. 2F, 2G) just based on physical manifestations [47][48][49][50] .…”

Section: Diagnostic Criteriamentioning

confidence: 99%

Diagnosis and Management of Sitosterolemia 2021

Tada

Nomura

Ogura

et al. 2021

JAT

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“…Genetic testing can differentiate other phenocopies, such as sitosterolemia 32) , autosomal recessive hypercholesterolemia (ARH) 33) , and cerebrotendinous xanthomatosis 34) . Differential diagnosis of these conditions is critically important because the optimal treatment strategy is different for different diagnoses.…”

Section: Genetic Diagnosis Of Fh: Is It Necessary and Why?mentioning

confidence: 99%

Challenges of Precision Medicine for Atherosclerotic Cardiovascular Disease Based on Human Genome Information

Tada

Usui

Sakata

et al. 2021

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The official journal of the Japan Atherosclerosis Society and the Asian Pacific Society of Atherosclerosis and Vascular Diseases Review Precision or personalized medicine is currently gaining a lot of attention. Clinical evidence for its effectiveness has been established based on randomized clinical trials accounting for classical risk factors, such as hypertension, diabetes, and serum lipids. However, besides such classical risk factors, the genetic background should be considered, at least for heritable traits, including atherosclerotic cardiovascular disease (ASCVD). Such classical risk factors are almost always incidents that have already occurred in which it may be too late to start treatment, instead of indicators of presymptomatic state. Human genome information is associated with most traits, including ASCVD. Two methods of implementing precision medicine for ASCVD using human genome information are currently being investigated: the use of rare genetic variations that have large effect sizes and polygenic risk scores that are composed of multiple common genetic variations. This review article emphasizes the importance of clinical as well as genetic diagnoses when implementing precision medicine. Precision medicine should be considered based on comprehensive genetic analyses, encompassing rare to common genetic variations. is strongly associated with premature ASCVD 4). A single loss-of-function genetic mutation in the LDL receptor gene is associated with ASCVD via elevation of LDL cholesterol because LDL cholesterol is one of the causal factors of ASCVD 5). However, there are a substantial number of people who are at extremely high risk for inherited ASCVD that is not associated with serum lipids. Causal links between biology and ASCVD development in such inherited risk factors exist. Aim The following review describes conditions beginning with FH in which precision medicine for ASCVD seems to be quite effective, to other conditions in which precision medicine for ASCVD is currently being rigorously examined.

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Prominent Tendon Xanthomas and Abdominal Aortic Aneurysm Associated with Cerebrotendinous Xanthomatosis Identified Using Whole Exome Sequencing

Cited by 13 publications

References 11 publications

Familial variability of cerebrotendinous xanthomatosis lacking typical biochemical findings

Familial variability of cerebrotendinous xanthomatosis lacking typical biochemical findings

Diagnosis and Management of Sitosterolemia 2021

Challenges of Precision Medicine for Atherosclerotic Cardiovascular Disease Based on Human Genome Information

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