A case of cerebrotendinous xanthomatosis with brain and spinal involvement without tendon xanthomas: Identification of a novel mutation of the CYP27A1 gene

J Clin Lipidol. May-Jun 2022;16(3):281-285. doi: 10.1016/j.jacl.2022.03.011.

PMID: 35428606

Christos Stenos, Konstantinos Kalafatakis, Pantelis Constantoulakis, Katerina Zekiou, Anna Margoni, Panagiota Kardara, Aspasia Terentiou, Georgios Stouraitis, Georgios Nikolaou

Highlights: This case report emphasizes the necessity of keeping a high index of suspicion as the key to a timely diagnosis of cerebrotendinous xanthomatosis (CTX), which has a clinical diversity and, if detected early, the favorable treatment response.

Abstract

Background: Cerebrotendinous xanthomatosis (CTX) is a rare inherited disorder of the alternative pathway of bile acid biosynthesis, due to mutation(s) of the gene CYP27A1, leading to sterol 27-hydroxylase deficiency. The latter results in a systematic deposition of cholestanol and cholesterol to the central nervous system and tendons, premature cataract, as well as the manifestation of systematic symptoms, such as chronic diarrhea, osteoporosis, and premature atherosclerosis. Due to its marked clinical heterogeneity, prompt diagnosis of this disorder is challenging.

Methods: A case of a 38-year-old male with gait difficulty, a progressive deterioration in ambulation, several episodes of vertigo and episodic diarrhea was presented. Clinical history revealed neonatal jaundice, juvenile bilateral cataracts, borderline intellectual capacity, hypothyroidism, testicular cancer. Magnetic resonance imaging demonstrated increased T2-weighted signal in internal capsules, midbrain, cerebellum, and spinal cord. Electrodiagnostic study showed mixed polyneuropathy. Genetic analysis revealed a novel, biallelic, most likely pathogenic mutation, in gene CYP2A1 (c.1410_1411del). Plasma sterol profiling confirmed the diagnosis of CTX.

Results: The patient was treated with chenodeoxycholic acid and one year later, he shows a progressive improvement of gait, normalization of plasma sterol biochemistry and electrophysiological parameters.

Conclusion: This case highlights the importance of maintaining a high index of suspicion as the key to an early diagnosis of CTX, taking into consideration its clinical variability and, if promptly identified, the good response to treatment.

Keywords: CYP27A1, Case report, Cerebrotendinous xanthomatosis, Cholestanol, Electrodiagnostic study, MRI, Suspicion index