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A Rare Form of Lipid Metabolic Encephalopathy

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 27-year-old Asian man was found with painless masses of about 5.1 cm in diameter that appeared on both Achilles tendons 10 years ago. Two years prior, he had no obvious inducement and gradually developed indifference, glassy eyes, lethargy, and poor memory. One year prior, the patient’s personality changed dramatically, with notably decreased memory formation but intact short-term memory. He was short-tempered, irritable, hyperactive, and exhibited slight balance instability while walking. On admission, physical examination showed unstable balance while walking in a straight line, positive ankle clonus bilaterally, positive Babinski sign bilaterally, positive Chaddock sign bilaterally, positive Romberg sign, and painless lumps of about 8.2 cm in diameter in both Achilles tendons. Routine laboratory test results showed that the patient’s triglyceride level was elevated at 342.48 mg/dL (to convert to millimoles per liter, multiply by 0.0013 mg/dL; normal levels are considered to be 30.97-150.44 mg/dL). A brain magnetic resonance imaging (MRI) indicated multiple bilateral, symmetric abnormal signals in the genus of the internal capsules, posterior limbs of internal capsules, cerebral peduncles, pons, and cerebellar dentate nuclei (Figure, A). Genetic testing indicated a known pathogenic mutation c.1214G>A (p.Arg405Gln; Hom) in the CYP27A1 gene. An MRI of the ankle joints revealed an enlargement of the left Achilles tendon with abnormal signal, and the right Achilles tendon was circumscribed by a fusiform enlargement with abnormal signal (Figure, B).

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C. Cerebrotendinous xanthomatosis

The brain MRI indicated multiple symmetrical strips and slightly longer T1 and T2 signals in the indicated regions. Fluid-attenuated inversion recovery indicated high signal (Figure, A) but enhanced MRI did not show enhanced signal. The N-acetylaspartate to creatine ratio decreased, and the chlorine to creatine ratio increased. There were no hemorrhagic foci or hemosiderin deposits in susceptibility-weighted imaging. The patient underwent CYP27A1 gene detection because the patient presented with encephalopathy with bilateral Achilles masses, suggesting a possible mutation of c.1214G>A (p.Arg405Gln; Hom). The patient’s various clinical manifestations and abnormal intracranial signals could not be explained as only frontotemporal dementia. Furthermore, there were no Kayser-Fleischer rings in the fundus of the eyes, and a normal serum copper blue protein test result excluded Wilson disease. All autoimmune antibodies tested negative, which did not support autoimmune encephalitis. As a result, a diagnosis of cerebrotendinous xanthomatosis (CTX) was made.

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Article Information

Corresponding Author: You-Dong Wei, MD, Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Rd, Yuzhong District, Chongqing 400016, China (havonewei@163.com).

Published Online: October 21, 2019. doi:10.1001/jamaneurol.2019.3551

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient’s mother for granting permission to publish this information.

References
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2.
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3.
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5.
Stelten  BML, Bonnot  O, Huidekoper  HH,  et al.  Autism spectrum disorder: an early and frequent feature in cerebrotendinous xanthomatosis.  J Inherit Metab Dis. 2018;41(4):641-646. doi:10.1007/s10545-017-0086-7PubMedGoogle ScholarCrossref
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