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Year : 2019  |  Volume : 29  |  Issue : 3  |  Page : 332-334
Cerebrotendinous xanthomatosis - A case report

Department of Radiodiagnosis, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India

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Date of Submission22-Nov-2018
Date of Acceptance10-Sep-2019
Date of Web Publication30-Oct-2019


Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder resulting from a defective enzyme in bile acid synthesis pathway leading to neurological, ocular, vascular, and musculoskeletal symptoms from deposition of cholestanol and cholesterol in these tissues. We present clinical and imaging features of a 32-year-old female who presented with mental retardation, gait instability and swelling along posterior aspect of both ankles. Imaging studies were performed which revealed spectrum of CTX findings in brain and tendons. Subsequently the diagnosis was confirmed by biopsy and laboratory tests.

Keywords: Cerebrotendinous xanthomatosis; cholestanol; dentate nucleus

How to cite this article:
Parry AH, Wani AH, Bashir M, Gojwari TA. Cerebrotendinous xanthomatosis - A case report. Indian J Radiol Imaging 2019;29:332-4

How to cite this URL:
Parry AH, Wani AH, Bashir M, Gojwari TA. Cerebrotendinous xanthomatosis - A case report. Indian J Radiol Imaging [serial online] 2019 [cited 2020 Feb 23];29:332-4. Available from:

   Introduction Top

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder resulting from a defective enzyme in bile acid synthesis pathway with deposition of cholestanol and cholesterol in brain, tendons, soft tissues and eyes leading to cerebellar dysfunction, early cataract formation, tendon, and soft tissue xanthomas. Around 300 cases of CTX have been reported worldwide to date. The disease is potentially treatable with chenodeoxycholic acid. Early diagnosis and treatment is essential to prevent the neurological sequelae of the disease.

   Case History Top

A 32-year-old, mentally retarded female presented with gait instability and right malar eminence swelling as well as swelling along the posterior aspect of both ankle joints. Patient had undergone surgery for cataracts in both eyes 10 years back. On examination patient was found to have ataxia, soft, non-tender swelling along the posterior aspect of both ankle joints, as well as right malar emminence [Figure 1]A. A preliminary diagnosis of cerebrotendinous xanthomatosis was made and evaluation was started.
Figure 1 (A and B): Photograph of bilateral ankles revealing swelling along the posterior aspect of both ankles (A) with corresponding lateral radiograph of both ankles revealing soft tissue radio-opacities posterior to calcaneal bones and tibia in the region of Achilles tendons (B)

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Lipid profile revealed total cholesterol of 306 mg/dl (LDL 205 mg/dl, VLDL 46mg/dl, HDL 55 mg/dl) and triglycerides of 526 mg/dl. Rest of the blood chemistry was normal. Radiograph of ankle joints revealed soft tissue swellings along the posterior aspect of both ankle joints and calcaneal bones [Figure 1]B. MRI of ankle joints revealed fusiform enlargement of bilateral Achilles tendons with signal intensity similar to muscle with speckled appearance on axial images consistent with tendinous xanthomatosis [Figure 2]. MRI brain revealed hyperintensity of bilateral dentate nuclei, deep cerebellar white matter with hyperintensity of posterior limbs of internal capsules on T2W and FLAIR images with corresponding hypointensity on T1W images [Figure 3]. Susceptibility weighted images [Figure 4]C revealed comma shaped hypointense signal of bilateral dentate nuclei. Hyopintense T1W and T2W round lesion was found in subcutaneous tissues of right malar eminence [Figure 4]A and [Figure 4]B which was subjected to FNAC which revealed a xanthoma [Figure 4]D. Serum cholestanol levels were raised (14 1 micromole/liter).
Figure 2 (A-D): Sagittal proton density image (A) and T1-weighted image (B) showing diffuse enlargement of Achilles tendon with axial proton density (C) and MEDIC (D) showing enlarged Achilles tendon with widely spaced tendon fibers interposed with fat (speckled appearance)

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Figure 3 (A-D): Axial T2-weighted and FLAIR images (A and B) reveal hyperintensity of bilateral dentate nuclei and deep cerebellar white matter. Hyperintensity of posterior limb of bilateral internal capsules is also seen on T2-weighted and FLAIR images (C and D)

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Figure 4 (A-D): Axial T2-weighted and T1-weighted images (A and B respectively) reveal a hypointense nodule (arrows) in the subcutaneous tissues of right malar eminence. Susceptibility weighted image (C) reveal comma shaped hypointensity (arrow) in the region of bilateral dentate nuclei. High power view photomicrograph (D) reveals multiple giant cells and cholesterol crystals consistent with diagnosis of xanthoma

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With a combined spectrum of clinical, biochemical and radiological findings, a diagnosis of cerebrotendinous xanthomatosis(CTX) was made.

   Discussion Top

CTX is an autosomal recessive disorder characterized by defective sterol 27-hydroxylase enzyme which is responsible for conversion of cholesterol into bile acids (cholic and chenodeoxycholic acid). Defect in this enzyme pathway results in accumulation of precursors of bile acids namely cholestanol and bile alcohols.[1],[2],[3] Abnormally elevated cholesterol and cholestanol compounds get deposited in soft tissues leading to early cataract formation, soft tissue and tendon xanthomas, early atherosclerosis. Subnormal intelligence, learning difficulties, cerebellar dysfunction and neuropathy comprise the neurological spectrum of the disease. Serum cholesterol and cholestanol levels are elevated in CTX.[1],[3],[4] Diagnosis is clinched by the characteristic combination of neurological, ocular and musculoskeletal symptoms supplemented by neuroimaging and biochemical results. In CTX, MRI of brain reveals hyperintensity of dentate nuclei and deep cerebellar white matter on T2-weighted and FLAIR sequences with associated cerebellar atrophy. Microcalcifications can occur within dentate nuclei which can be demonstrated as hypointensity of dentate nuclei on susceptibility weighted imaging. Cerebral atrophy with T2W and FLAIR hyperintensity of supratentorial white matter and deep grey nuclei can also be seen. Involvement of internal capsule as T2W/FLAIR hyperintensity.[1],[2],[3],[5],[6] All these areas of signal intensity change exhibit increased diffusivity on DWI. Tendon xanthomascan be demonstrated by MRI as enlargement of tendons with hypointense signal intensity. Soft tissue xanthomas also exhibit hypointense signal intensity on both T1W and T2W images.

CTX has a myriad of differential diagnosis. It mimics hypercholesterolemia and sitosterolemia which share xanthoma as a clinical feature with it. Sitosterolemia is differentiated from CTX by absence of neurological symptoms and cataract formation. Hypercholesterolemia is characterized by formation of xanthomas with elevated cholesterol levels but with normal cholestanol levels. CTX also resembles Marinesco-Sjogren syndrome which also presents with triad of cataract formation, ataxia and mental retardation but the absence of tendon xanthomas and presence of scoliosis, short small bones of hand and feet reliably differentiate this disorder from CTX. On neuroimaging those disorders which exhibit hyperintensity of dentate nuclei on T2W images need to be differentiated from CTX. These include metronidazole toxicity and acutely decompensated maple syrup urine disease. These two disorders present with acute encephalopathy unlike CTX which has an insidious presentation.[1],[5],[7]

Treatment consists of chenodeoxycholic acid which suppresses the formation of cholestanol. Treatment must be started at the earliest to halt the neurological deterioration.[1],[4],[7],[8] Though this is a typical case of CTX but the fact that patient had not been diagnosed previously has led to permanent neurological damage in the form of subnormal intelligence and cerebellar ataxia. The fact that patient was operated for juvenile cataracts a decade back should have alerted the physician to ascertain the etiology of early cataract formation and early institution of appropriate therapy to avert the neurological sequelae of this otherwise treatable condition.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Gerrish AC, Gaba S. Case 239: Cerebrotendinousxanthomatosis. Radiology 2017;282:916-21.  Back to cited text no. 1
Barkhof F, Verrips A, Wesseling P, van der Knaap MS, van Engelen BG, Gabreëls FJ, et al. Cerebrotendinousxanthomatosis: The spectrum of imaging findings and the correlation with neuropathologic findings. Radiology 2000;217:869-76.  Back to cited text no. 2
Pudhiavan A, Agrawal A, Chaudhari S, Shukla A. Cerebrotendinousxanthomatosis-The spectrum of imaging findings. J Radiol Case Rep 2013;7:1.  Back to cited text no. 3
Gaikwad SB, Garg A, Mishra NK, Gupta V, Srivastava A, Sarkar C. Cerebrotendinousxanthomatosis: Neuroimaging findings in two siblings from an Indian family. Neurol India 2003;51:401.  Back to cited text no. 4
Chakraverty S, Griffiths PD, Walls TJ, McAllister VL. Cerebrotendinousxanthomatosis in two sisters: Case reports and MR imaging. Clin Radiol 1995;50:117-9.  Back to cited text no. 5
Inglese M, DeStefano N, Pagani E, Dotti MT, Comi G, Federico A, et al. Quantification of brain damage in cerebrotendinousxanthomatosis with magnetization transfer MR imaging. AJNR Am J Neuroradiol 2003;24:495-500.  Back to cited text no. 6
Nie S, Chen G, Cao X, Zhang Y. Cerebrotendinousxanthomatosis: A comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management. Orphanet J Rare Dis 2014;9:179.  Back to cited text no. 7
Makary MS, Kisanuki YY, Amin NN, Slone HW. Teaching neuroimages: Cerebrotendinousxanthomatosis: A rare treatable adult-onset lipid storage disease. Neurology 2018;90:e637-8.  Back to cited text no. 8

Correspondence Address:
Dr. Arshed Hussain Parry
Department of Radiodiagnosis, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar - 190 011, Jammu and Kashmir
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijri.IJRI_444_18

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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