First case series of Polish patients with cerebrotendinous xanthomatosis and systematic review of cases from the 21st century

Clin Genet. 2022 Feb;101(2):190-207. doi: 10.1111/cge.14079.

PMID: 34689324

Magdalena Badura-Stronka, Adam Sebastian Hirschfeld, Anna Winczewska-Wiktor

Highlights: This is the widest review of CTX (cerebrotendinous xanthomatosis) cases reported between the years 2000-2021. This study reports the largest cohort of Polish patients ever published, with the identification of two hot-spot mutations.

Abstract

Background: CTX (cerebrotendinous xanthomatosis) is an inborn metabolic disorder caused by recessive variants in the cytochrome P450 CYP27A1 gene. CTX is linked to persistent diarrhea in children as well as the classic triad of juvenile cataracts, Achilles tendon xanthomas, and progressive ataxia. It's currently one of the few inherited neurometabolic disorders with a therapeutic option. It's possible that the diagnosis will be delayed, resulting in permanent neurological impairment.

Methods and results: A retrospective examination of the clinical features and diagnostic findings in six Polish CTX patients. Additional analysis of symptoms and pathogenic variants from 568 CTX patients and case series accessible over the last 20 years. To our knowledge, this is the most comprehensive study of CTX cases documented from 2000 to 2021. With the discovery of two hot-spot mutations, we present the biggest cohort of Polish patients ever published. We discovered significant disparities in clinical symptoms and the localization of variants within the gene between Asian and non-Asian populations after reviewing 568 cases.

Conclusion: These findings could make molecular testing more accessible to Polish and Asian communities. Better CTX screening and increased awareness are unquestionably required.

Keywords: CTX, CYP27A1, Polish, cerebrotendinous xanthomatosis