Targeted genetic testing crucial in identifying rare genetic disorder in patients with early-onset cataracts

A recent study has successfully identified cases of Cerebrotendinous xanthomatosis (CTX) in a population of patients with early-onset cataracts. By conducting genetic testing on individuals with elevated plasma cholestanol (PC) levels and positive urinary bile alcohol (UBA) tests, the researchers confirmed the diagnosis of CTX in a subset of patients.

The study highlights the importance of early detection and genetic testing in populations with a higher prevalence of CTX, allowing for timely interventions and improved management of the disorder.

CTX is an extremely rare autosomal recessive bile acid synthesis disorder caused by mutations in the CYP27A1 gene, which is responsible for bile acid synthesis.

CTX is characterized by the accumulation of PC in various tissues due to impaired function of the CYP27A1 gene. This accumulation typically occurs during early childhood and leads to a range of clinical signs, including infantile diarrhea, early-onset bilateral cataracts, and neurological deterioration.

In the study, researchers enrolled patients diagnosed with early-onset, apparently idiopathic, bilateral cataracts between the ages of 2 and 21 years. The researchers aimed to identify individuals with a higher prevalence of CTX within this specific population. Genetic testing was performed on patients with elevated levels of plasma cholestanol (PC) and positive UBA tests to confirm the diagnosis of CTX.

Out of the 426 patients who completed the study, 26 met the criteria for genetic testing based on their PC levels (PC ≥ 0.4 mg/dL) and positive UBA tests. Genetic analysis confirmed that 4 of these patients indeed had CTX, highlighting the significance of early detection in identifying affected individuals who may require treatment and intervention.

The study found that the prevalence of CTX was 0.9% among all enrolled patients. However, when considering only the patients who met the criteria for genetic testing, the prevalence increased to 15.4%. These results emphasize the importance of targeted genetic testing in populations with a higher likelihood of having CTX, such as individuals presenting with early-onset bilateral cataracts.

Reference
Freedman SF, Del Monte MA, Diva U, et al. Prevalence of Cerebrotendinous Xanthomatosis (CTX) Among Patients Diagnosed With Early-Onset Idiopathic Bilateral Cataracts: Final Analysis. J AAPOS. 2023;S1091-8531(23)00119-2. doi: 10.1016/j.jaapos.2023.04.013. Epub ahead of print. PMID: 37321343.