18 year female presented with bilateral thickened Achilles tendons & left infrapatellar swelling. She was operated for similar complaints in bilateral elbows in the past. Concurrently Patient was on treatment with antiepileptic for seizure disorder, had history of delayed milestones and learning disabilities. Also had cataract surgery bilaterally in the past.
On clinical examination, patient had scar marks over both elbows from the previous surgery (A), thickened tendon of Achilles bilaterally (B, C) with palpable subcutaneous infrapatellar lesion (D) Fig1.A,B,C,D.
As a preliminary step, A radiograph of the ankle joints was done which demonstrated soft tissue thickening posterior to the ankle. No evidence of soft tissue calcification or bone abnormalities.Fig.2
Subsequently, US examination was performed. This demonstrated thickening of the Achilles tendons bilaterally, to up to 23.6 mm (Fig 3A right Achilles tendon, Fig 3B left Achilles tendon), whole tendon is echogenic and has lost the typical anisotropic fibre pattern. US examination of the infrapatellar tendon (Fig 3C) demonstrated a nodular lesion within the subcutaneous tissue, with no associated vascularity, interpreted as a cutaneous xanthoma
Concurrently, MRI of the bilateral ankles & brain revealed Fig.4A&4B. Fat sat PDFSw sagittal images show diffuse fatty infiltration of the tendon with low-intensity tendon bundles interspersed within i.e, striated pattern. Fig4C.T1w image showing hypointense tendon compared to muscles demonstrating thickening Fig4D. STIR axial image reveals fusiform enlargement of the tendon
Background
Cerebro-tendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disease associated with abnormally high cholestanol levels. Cholestanol is a derivate of cholesterol. It is a key feature of the disease that there is cholesterol and cholestanol deposit in cells and membranes notably in the brain, tendons, eyes, arteries and is responsible for a broad spectrum of clinical manifestations. It is manifested by subtle neurological and non-neurological symptoms. Diagnosis is usually delayed but early diagnosis and replacement therapy can prevent debilitating neurological sequelae.
Clinical perspective
Cerebro-tendinous xanthomatosis (CTX) is an exceptionally rare condition in Indian subcontinent, [1] however, it is potentially treatable if diagnosed. CTX disease caused by mutations in the CYP27A1 gene.[2, 3]. This gene encodes for the mitochondrial enzyme sterol 27-hydroxylase, which is involved in bile acid synthesis. This genotype has previously been described in an adult female with classical symptoms of CTX.[2] "Clinical signs and symptoms include juvenile cataracts, progressive neurologic dysfunction, and mild pulmonary insufficiency. THESE ARE unique symptoms that distinguish CTX from other lipid storage disorders which might also present with xanthomas and cardiovascular diseases.[3] DESCRIBED SYMPTOMS are adult-onset progressive neurological dysfunction (i.e., ataxia, dystonia, dementia, epilepsy, psychiatric disorders, peripheral neuropathy, and myopathy) and premature non-neurologic manifestations (i.e., tendon xanthomas, childhood-onset cataracts, infantile-onset diarrhoea, premature atherosclerosis, osteoporosis, and respiratory insufficiency). [4,5] The classical symptoms and signs, elevated levels of cholestanol and bile alcohols in serum and urine, and the mutation in the CYP27A1 gene confirms the diagnosis of CTX [8,9].
Imaging perspective
Brain MRI shows hyper-intensity in bilateral dentate nuclei of the cerebellum a [6,7], MRI of the bilateral ankles shows thickened achilles tendon with striated pattern of hyper-intense signals on PDFS sagittal images suggesting cholestenol deposition in these areas.
Above findings can be prognostic marker of disease, an increase hyperintensities in the findings suggesting worsening or a decrease in the findings indicating good favourable prognosis.
Outcome
Early diagnosis and long-term treatment with chenodeoxycholic acid (CDCA) [9,10] normalizes bile acid synthesis, normalizes plasma and CSF concentration of cholestanol, and improves neurophysiologic findings. Inhibitors of HMG-CoA reductase alone or in combination with CDCA are also effective in decreasing cholestanol. [11] Secondary complications can be prevented with Calcium and vitamin D supplementation to tackle osteoporosis. Annual Surveillance of neurologic and neuropsychological evaluation, plasma cholestanol concentration, brain MRI, echocardiogram, and assessment of total body density (TBD) is done in follow-up of disease. [11] Genetic counselling should be done as CTX is inherited in an autosomal recessive manner. Carrier testing for at-risk family members and prenatal testing for pregnancies should be done.[11]
Take home message
Our present case emphasizes the fact that early-age bilateral tendocalcaneal xanthoma with bilateral cataracts, imaging findings in cerebellum with typical histopathological findings from biopsy are pointers toward the diagnosis of cerebrotendinous xanthomatosis.[5, 6, 11]
Written informed patient consent for publication has been obtained
Cerebro-tendinous xanthomatosis (CTX)
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Based on the provided X-ray, ultrasound, and MRI examinations, the main radiological features are as follows:
Taking into account the patient's history (bilateral congenital cataract surgery in childhood, neurological symptoms, learning difficulties, seizures, and thickening of both Achilles and other tendons) along with the imaging findings, the following differential diagnoses are considered:
Considering the patient’s age, neurological symptoms (seizures and intellectual disability), childhood bilateral cataract surgery, bilateral multiple tendon xanthoma-like thickening, and the characteristic signal changes in the dentate nuclei, the most likely diagnosis is:
Cerebrotendinous Xanthomatosis (CTX).
For further confirmation, additional tests such as serum or cerebrospinal fluid cholestanol measurements and genetic testing (screening for CYP27A1 mutations) can be performed.
1. Pharmacological and Surgical Treatment:
2. Rehabilitation and Exercise Prescription:
FITT-VP Principle Example:
Frequency: 3–5 times per week
Intensity: Low to moderate
Time: About 20 minutes per session, with gradual increases based on tolerance
Type: Aerobic exercises combined with light resistance training
Volume and Progression: Adjust training volume and exercise format every 2–4 weeks according to clinical improvements and individual tolerance
This report is a reference analysis based on the available imaging and medical history. It does not replace in-person consultations, genetic testing, or comprehensive assessments and guidance from qualified healthcare professionals. Specific treatment plans should be conducted under specialist supervision according to the individual patient's condition.
Cerebro-tendinous xanthomatosis (CTX)
