Teaching Case

23-year-old mentally retarded female patient, presented with a history of seizures since childhood. On examination, the patient had cataracts bilaterally and soft tissue swellings along the posterior aspect of both ankles. No other significant family or personal history.

Figure 1

Radiographs of ankles showed soft tissue lesions along the posterior aspect of both ankles.

Figure 2

Magnetic resonance imaging confirmed the lesion was arising from the Achilles tendon, hyperintense on T1 WI and T2 WI and suppressed on fat saturation sequences.

Figure 3

MRI of the brain showed generalized age-inappropriate cerebral and cerebellar atrophy.

Abnormal T2 hyperintensity and T1 hypointensity was seen within the dentate nucleus and in the surrounding deep cerebellar white matter. Intense blooming was noted in bilateral dentate nuclei. White matter hyperintensity was seen in the brainstem.

Figure 4

MR spectroscopy at TE 30 demonstrates lipid peaks at 0.9 and 1.3 ppm and an increase in the mIns peak.

Figure 5

MR spectroscopy at TE 135 shows an inverted lactate peak and a decreased NAA peak.

Figure 6

Background

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder with less than 400 cases reported worldwide [1]. The disease is eponymously named Van Bogaert-Scherer-Epstein disease. 

CTX is characterized by abnormal deposition of cholesterol and cholestanol in multiple soft tissues, caused by mutations in the CYP27 gene. This gene encodes for sterol 27-hydroxylase, a key enzyme in the biosynthesis of bile acids located on the inner membrane of the mitochondria. As a result, primary bile acids cholic and chenodeoxycholic acid are not synthesized which induces the up-regulation of cholesterol 7α-hydroxylase. This causes the accumulation of cholestanol and bile alcohols in the various body tissues namely, the lens, brain and muscle tendons leading to the constellation of symptoms [2].

Clinical Perspective

Systemic features

• Gastrointestinal tract- Chronic diarrhoea
• Orbit- Cataracts
• Cardiovascular system- Premature atherosclerosis and lipomatous hypertrophy of the interatrial septum
• Skeletal system- Osteopenia
• Xanthomas [3]

Neurological features

• Cognitive impairment
• Spasticity
• Seizures
• Peripheral neuropathy [3]

Imaging Perspective

Bilateral hyperintensity of the dentate nuclei and cerebral and cerebellar white matter. Changes in brain computed tomography (CT) and magnetic resonance imaging (MRI) include diffuse brain and cerebellar atrophy, white matter signal alterations, and bilateral focal cerebellar lesions [3].

Blooming is typically noted in these areas of hyperintensity. MRI may show a characteristic trilaminar appearance of the dentate [4].

MR spectroscopy shows decreased N-Acetylaspartate and increased lactate, indicative of widespread brain mitochondrial dysfunction [5].

Tendon xanthomas were inhomogeneously hypo- to isointense on T1W images and hypo- to isointense on T2W images. Achilles tendons were most frequently involved [6].

Outcome and Management of Patients

Long-term treatment with HMGCoA reductase inhibitors and CDCA (750 mg/day in adults) normalizes bile acid synthesis (leading to the disappearance of abnormal metabolites from serum, bile, and urine), normalizes plasma and CSF concentration of cholestanol by suppressing cholestanol biosynthesis, and other clinical manifestations including osteoporosis [7]. Treatment with chenodeoxycholic acid should be continued even during pregnancy [3].

Teaching Point

Imaging plays an important role in the diagnosis of CTX. Early diagnosis of CTX is important as these patients benefit from replacement therapy of chenodeoxycholic acid.

Written informed patient consent for publication has been obtained.