Study highlights critical diagnostic delays in CTX, urges early screening

The largest cerebrotendinous xanthomatosis case series from a single orthopedic clinic underscores the importance of considering CTX in patients presenting with xanthomas despite normal cholesterol levels. The findings advocate for genetic testing, serum cholestanol level assessment, and sibling examination for early and accurate diagnosis.

Despite symptoms typically emerging in infancy, CTX diagnosis is frequently delayed, emphasizing the need for heightened awareness among healthcare providers.

The research team retrospectively reviewed the clinical, laboratory, radiological, and genetic data of 8 patients from 4 families, admitted between 2017 and 2022 due to bilateral Achilles tendon xanthomas. A novel CYP27A1 gene variant (c.670_671delAA) was identified in 3 patients who also exhibited peripheral neuropathy and bilateral pes cavus.

The mean age of the patients was 37 years, with an average symptom onset at 9.25 years and an initial diagnosis at 33.75 years, reflecting a diagnostic delay of 24.5 years. Osteoporosis was present in 1 patient and osteopenia in 4. Five patients had a history of bilateral cataracts, 3 experienced early-onset chronic diarrhea, and another 3 had ataxia. Two patients had epilepsy, while 7 showed behavior-personality disorders. All patients had low intelligence levels.

“We suggest that patients with normal cholesterol levels presenting with xanthoma being genetically analyzed by testing at their serum cholestanol level, and that all siblings of patients diagnosed with CTX be examined,” the researchers concluded.

Reference
Köroğlu M, Karakaplan M, Gündüz E, et al. Cerebrotendinous Xanthomatosis patients with late diagnosed in single orthopedic clinic: two novel variants in the CYP27A1 gene. Orphanet J Rare Dis. 2024;19(1):53. doi: 10.1186/s13023-024-03082-4. PMID: 38336741; PMCID: PMC10858589.