Prospective cholestanol screening of cerebrotendinous xanthomatosis among patients with juvenile-onset unexplained bilateral cataracts.
Cataract
Cerebrotendinous xanthomatosis
Cholestanol
Inborn errors of metabolism
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
13 12 2022
13 12 2022
Historique:
received:
13
06
2022
accepted:
07
12
2022
entrez:
13
12
2022
pubmed:
14
12
2022
medline:
16
12
2022
Statut:
epublish
Résumé
Cerebrotendinous xanthomatosis (CTX) is a rare genetic disorder related to CYP27A1 biallelic mutations, leading to decreased synthesis of bile acids and increased cholestanol. Juvenile bilateral cataracts are one of the most common findings in the disease, frequently occurring before the onset of neurological manifestations. While early treatment with chenodeoxycholic acid can prevent the onset of neurological impairment, poor awareness of CTX accounts for a markedly delayed diagnosis. The objective of this study was to evaluate the utility of plasma cholestanol analysis at the moment of cataract diagnosis and before the onset of neurological impairment in CTX. Multicenter prospective cohort study of patients with juvenile-onset unexplained bilateral cataracts recruited from seven French ophthalmology departments. Plasma cholestanol analysis was performed at diagnosis from January 2018 to January 2020. CYP27A1 genetic testing was performed at the ophthalmologist's discretion. Cholestanol levels were compared with those of a similar population of patients without cataracts (control cohort). 30 patients were finally recruited, with a mean age at cataract diagnosis of 7.1 years (± 4.8 SD, range 1-19 years). One patient had a very high cholestanol level (68 μmol/L, reference < 10) and carried two pathogenic heterozygous mutations in CYP27A1 confirming CTX. This patient was a 19-year-old female, reporting chronic diarrhea only in childhood, and diagnosed with bilateral posterior cataracts with cortical fleck-like opacities. Therefore, the incidence of CTX in our cohort of patients was 3.3%. Five further patients (5/29; 17.2%) had moderate elevations of cholestanol level (between 10.3 and 16.5 μmol/L), compared to 12/286 (4.2%) in the control cohort (p = 0.014) after adjustment for age. Our study argue for the relevance of plasma cholestanol CTX screening in all patients with juvenile-onset unexplained cataracts, even without other CTX identified manifestations. Whether moderate elevations of plasma cholestanol unrelated to CTX may be a risk factor for bilateral cataracts occurrence needs further examination.
Sections du résumé
BACKGROUND
Cerebrotendinous xanthomatosis (CTX) is a rare genetic disorder related to CYP27A1 biallelic mutations, leading to decreased synthesis of bile acids and increased cholestanol. Juvenile bilateral cataracts are one of the most common findings in the disease, frequently occurring before the onset of neurological manifestations. While early treatment with chenodeoxycholic acid can prevent the onset of neurological impairment, poor awareness of CTX accounts for a markedly delayed diagnosis. The objective of this study was to evaluate the utility of plasma cholestanol analysis at the moment of cataract diagnosis and before the onset of neurological impairment in CTX.
METHODS
Multicenter prospective cohort study of patients with juvenile-onset unexplained bilateral cataracts recruited from seven French ophthalmology departments. Plasma cholestanol analysis was performed at diagnosis from January 2018 to January 2020. CYP27A1 genetic testing was performed at the ophthalmologist's discretion. Cholestanol levels were compared with those of a similar population of patients without cataracts (control cohort).
RESULTS
30 patients were finally recruited, with a mean age at cataract diagnosis of 7.1 years (± 4.8 SD, range 1-19 years). One patient had a very high cholestanol level (68 μmol/L, reference < 10) and carried two pathogenic heterozygous mutations in CYP27A1 confirming CTX. This patient was a 19-year-old female, reporting chronic diarrhea only in childhood, and diagnosed with bilateral posterior cataracts with cortical fleck-like opacities. Therefore, the incidence of CTX in our cohort of patients was 3.3%. Five further patients (5/29; 17.2%) had moderate elevations of cholestanol level (between 10.3 and 16.5 μmol/L), compared to 12/286 (4.2%) in the control cohort (p = 0.014) after adjustment for age.
CONCLUSION
Our study argue for the relevance of plasma cholestanol CTX screening in all patients with juvenile-onset unexplained cataracts, even without other CTX identified manifestations. Whether moderate elevations of plasma cholestanol unrelated to CTX may be a risk factor for bilateral cataracts occurrence needs further examination.
Identifiants
pubmed: 36514115
doi: 10.1186/s13023-022-02591-4
pii: 10.1186/s13023-022-02591-4
pmc: PMC9749289
doi:
Substances chimiques
Cholestanol
8M308U816E
Chenodeoxycholic Acid
0GEI24LG0J
Types de publication
Case Reports
Multicenter Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
434Informations de copyright
© 2022. The Author(s).
Références
J AAPOS. 2021 Oct;25(5):269.e1-269.e6
pubmed: 34600103
J Clin Lipidol. 2015 Nov-Dec;9(6):807-816
pubmed: 26687702
J Ophthalmol. 2011;2011:471947
pubmed: 21577274
J AAPOS. 2017 Dec;21(6):505-507
pubmed: 29079218
Eye (Lond). 2018 Nov;32(11):1794-1795
pubmed: 29988074
Ophthalmology. 2016 Jan;123(1):217-20
pubmed: 26233629
J Inherit Metab Dis. 2014 May;37(3):421-9
pubmed: 24442603
J Inherit Metab Dis. 2017 Nov;40(6):771-781
pubmed: 28980151
JAMA Ophthalmol. 2019 Nov 01;137(11):1312-1316
pubmed: 31536098
Clin Neuropharmacol. 2013 May-Jun;36(3):78-83
pubmed: 23673909
Lancet. 2017 Aug 5;390(10094):600-612
pubmed: 28242111
Neurology. 2019 Jan 8;92(2):e83-e95
pubmed: 30530799
Ophthalmology. 2013 May;120(5):956-60
pubmed: 23375591
J Pediatr Genet. 2014 Dec;3(4):219-27
pubmed: 27625879
J Inherit Metab Dis. 2002 Dec;25(8):629-34
pubmed: 12705493
Lipids Health Dis. 2019 Dec 30;18(1):235
pubmed: 31888647
Eye (Lond). 2016 Sep;30(9):1175-81
pubmed: 27315345