Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to <i>CYP27A1</i> Gene Mutation with Chenodeoxycholic Acid Therapy
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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/11/5/1430 |
| _version_ | 1827741928650702848 |
|---|---|
| author | Petar Brlek Luka Bulić David Glavaš Weinberger Jelena Bošnjak Tomislav Pavlović Svetlana Tomić Zdravka Krivdić Dupan Igor Borić Dragan Primorac |
| author_facet | Petar Brlek Luka Bulić David Glavaš Weinberger Jelena Bošnjak Tomislav Pavlović Svetlana Tomić Zdravka Krivdić Dupan Igor Borić Dragan Primorac |
| author_sort | Petar Brlek |
| collection | DOAJ |
| description | 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 <i>CYP27A1</i> 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. |
| first_indexed | 2024-03-11T03:55:04Z |
| format | Article |
| id | doaj.art-bd3056ac8d5241c1ab3f8d20cc3e8c74 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T03:55:04Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-bd3056ac8d5241c1ab3f8d20cc3e8c742023-11-18T00:36:59ZengMDPI AGBiomedicines2227-90592023-05-01115143010.3390/biomedicines11051430Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to <i>CYP27A1</i> Gene Mutation with Chenodeoxycholic Acid TherapyPetar Brlek0Luka Bulić1David Glavaš Weinberger2Jelena Bošnjak3Tomislav Pavlović4Svetlana Tomić5Zdravka Krivdić Dupan6Igor Borić7Dragan Primorac8St. Catherine Specialty Hospital, 10000 Zagreb, CroatiaSt. Catherine Specialty Hospital, 10000 Zagreb, CroatiaSt. Catherine Specialty Hospital, 10000 Zagreb, CroatiaSt. Catherine Specialty Hospital, 10000 Zagreb, CroatiaSt. Catherine Specialty Hospital, 10000 Zagreb, CroatiaSchool of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, CroatiaSchool of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, CroatiaSt. Catherine Specialty Hospital, 10000 Zagreb, CroatiaSt. Catherine Specialty Hospital, 10000 Zagreb, CroatiaCerebrotendinous 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 <i>CYP27A1</i> 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.https://www.mdpi.com/2227-9059/11/5/1430ataxiacerebrotendinous xanthomatosischenodeoxycholic acidcholestanolxanthomanext-generation sequencing |
| spellingShingle | Petar Brlek Luka Bulić David Glavaš Weinberger Jelena Bošnjak Tomislav Pavlović Svetlana Tomić Zdravka Krivdić Dupan Igor Borić Dragan Primorac Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to <i>CYP27A1</i> Gene Mutation with Chenodeoxycholic Acid Therapy Biomedicines ataxia cerebrotendinous xanthomatosis chenodeoxycholic acid cholestanol xanthoma next-generation sequencing |
| title | Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to <i>CYP27A1</i> Gene Mutation with Chenodeoxycholic Acid Therapy |
| title_full | Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to <i>CYP27A1</i> Gene Mutation with Chenodeoxycholic Acid Therapy |
| title_fullStr | Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to <i>CYP27A1</i> Gene Mutation with Chenodeoxycholic Acid Therapy |
| title_full_unstemmed | Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to <i>CYP27A1</i> Gene Mutation with Chenodeoxycholic Acid Therapy |
| title_short | Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to <i>CYP27A1</i> Gene Mutation with Chenodeoxycholic Acid Therapy |
| title_sort | successful treatment of a rare cholesterol homeostasis disorder due to i cyp27a1 i gene mutation with chenodeoxycholic acid therapy |
| topic | ataxia cerebrotendinous xanthomatosis chenodeoxycholic acid cholestanol xanthoma next-generation sequencing |
| url | https://www.mdpi.com/2227-9059/11/5/1430 |
| work_keys_str_mv | AT petarbrlek successfultreatmentofararecholesterolhomeostasisdisorderduetoicyp27a1igenemutationwithchenodeoxycholicacidtherapy AT lukabulic successfultreatmentofararecholesterolhomeostasisdisorderduetoicyp27a1igenemutationwithchenodeoxycholicacidtherapy AT davidglavasweinberger successfultreatmentofararecholesterolhomeostasisdisorderduetoicyp27a1igenemutationwithchenodeoxycholicacidtherapy AT jelenabosnjak successfultreatmentofararecholesterolhomeostasisdisorderduetoicyp27a1igenemutationwithchenodeoxycholicacidtherapy AT tomislavpavlovic successfultreatmentofararecholesterolhomeostasisdisorderduetoicyp27a1igenemutationwithchenodeoxycholicacidtherapy AT svetlanatomic successfultreatmentofararecholesterolhomeostasisdisorderduetoicyp27a1igenemutationwithchenodeoxycholicacidtherapy AT zdravkakrivdicdupan successfultreatmentofararecholesterolhomeostasisdisorderduetoicyp27a1igenemutationwithchenodeoxycholicacidtherapy AT igorboric successfultreatmentofararecholesterolhomeostasisdisorderduetoicyp27a1igenemutationwithchenodeoxycholicacidtherapy AT draganprimorac successfultreatmentofararecholesterolhomeostasisdisorderduetoicyp27a1igenemutationwithchenodeoxycholicacidtherapy |