Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to CYP27A1 Gene Mutation with Chenodeoxycholic Acid Therapy

Brlek, Petar; Bulić, Luka; Glavaš Weinberger, David; Bošnjak, Jelena; Pavlović, Tomislav; Tomić, Svetlana; Krivdić Dupan, Zdravka; Borić, Igor; Primorac, Dragan

doi:10.3390/biomedicines11051430

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Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to CYP27A1 Gene Mutation with Chenodeoxycholic Acid Therapy

by

Petar Brlek

^1,*

,

Luka Bulić

¹

,

David Glavaš Weinberger

¹

,

Jelena Bošnjak

¹,

Tomislav Pavlović

^1,2,3

,

Svetlana Tomić

^3,4,

Zdravka Krivdić Dupan

^3,4

,

Igor Borić

¹

and

Dragan Primorac

^{1,3,5,6,7,8,9,10,11,12,13}

¹

St. Catherine Specialty Hospital, 10000 Zagreb, Croatia

²

Department of Health Studies, University of Split, 21000 Split, Croatia

³

School of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia

⁴

University Hospital Centre, 31000 Osijek, Croatia

⁵

Medical School, University of Split, 21000 Split, Croatia

⁶

Department of Biochemistry & Molecular Biology, The Pennsylvania State University, State College, PA 16802, USA

⁷

The Henry C. Lee College of Criminal Justice and Forensic Sciences, University of New Haven, West Haven, CT 06516, USA

⁸

Medical School REGIOMED, 96450 Coburg, Germany

⁹

Medical School, University of Rijeka, 51000 Rijeka, Croatia

¹⁰

Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia

¹¹

Medical School, University of Mostar, 88000 Mostar, Bosnia and Herzegovina

¹²

National Forensic Sciences University, Gujarat 382007, India

¹³

University Hospital Centre Zagreb, 10000 Zagreb, Croatia

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Biomedicines 2023, 11(5), 1430; https://doi.org/10.3390/biomedicines11051430

Submission received: 31 March 2023 / Revised: 5 May 2023 / Accepted: 10 May 2023 / Published: 12 May 2023

(This article belongs to the Special Issue Lipid and Cholesterol Metabolism in Health and Disease: A Focus on the Cross-Talk between Peripheral Tissues and Central Nervous System)

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Abstract

Cerebrotendinous xanthomatosis (CTX) is a genetic disorder of the cholesterol metabolic pathway, most often associated with variants in the CYP27A1 gene. The dysregulation of cholesterol metabolism results in the accumulation of metabolites such as cholestanol, which has a predilection for neuronal tissue and tendons. The condition is treatable with chenodeoxycholic acid (CDCA), which halts the production of these metabolites. We present two adult brothers, without diagnosis, suffering from ataxia, general muscle weakness and cognitive deficits. Both brothers suffered from early onset cataracts, watery stools and thoracic kyphoscoliosis. Magnetic resonance imaging revealed hyperintense alterations in the central nervous system and intratendinous xanthomas in the Achilles tendons. A biochemical analysis showed elevated levels of cholestanol, lathosterol and 7-dehydrocholesterol. Their family history was negative for neurological and metabolic disorders. Genetic testing revealed a pathogenic CYP27A1 variant (c.1184+1G>A) in both brothers, confirming the diagnosis. The patients were started on CDCA therapy and have shown significant improvement at their follow-up examinations. Early diagnosis and treatment initiation in CTX patients is of great importance, as the significant reversal of disease progression can be achieved. For this reason, clinical genetic testing is necessary when it comes to patients with an onset of cataracts, chronic diarrhea, and neurological symptoms in early childhood.

Keywords: ataxia; cerebrotendinous xanthomatosis; chenodeoxycholic acid; cholestanol; xanthoma; next-generation sequencing

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MDPI and ACS Style

Brlek, P.; Bulić, L.; Glavaš Weinberger, D.; Bošnjak, J.; Pavlović, T.; Tomić, S.; Krivdić Dupan, Z.; Borić, I.; Primorac, D. Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to CYP27A1 Gene Mutation with Chenodeoxycholic Acid Therapy. Biomedicines 2023, 11, 1430. https://doi.org/10.3390/biomedicines11051430

AMA Style

Brlek P, Bulić L, Glavaš Weinberger D, Bošnjak J, Pavlović T, Tomić S, Krivdić Dupan Z, Borić I, Primorac D. Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to CYP27A1 Gene Mutation with Chenodeoxycholic Acid Therapy. Biomedicines. 2023; 11(5):1430. https://doi.org/10.3390/biomedicines11051430

Chicago/Turabian Style

Brlek, Petar, Luka Bulić, David Glavaš Weinberger, Jelena Bošnjak, Tomislav Pavlović, Svetlana Tomić, Zdravka Krivdić Dupan, Igor Borić, and Dragan Primorac. 2023. "Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to CYP27A1 Gene Mutation with Chenodeoxycholic Acid Therapy" Biomedicines 11, no. 5: 1430. https://doi.org/10.3390/biomedicines11051430

APA Style

Brlek, P., Bulić, L., Glavaš Weinberger, D., Bošnjak, J., Pavlović, T., Tomić, S., Krivdić Dupan, Z., Borić, I., & Primorac, D. (2023). Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to CYP27A1 Gene Mutation with Chenodeoxycholic Acid Therapy. Biomedicines, 11(5), 1430. https://doi.org/10.3390/biomedicines11051430

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Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to CYP27A1 Gene Mutation with Chenodeoxycholic Acid Therapy

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