Cataracts are 1 of 4 “hallmark manifestations” of cerebrotendinous xanthomatosis (CTX), a rare genetic disorder that affects the body’s ability to metabolize cholesterols.
During the National Lipid Association Scientific Sessions, Ernst Schaefer, MD; Andrea DeBarber, PhD; and P. Barton Duell, MD, presented information about the condition and the associated ocular implications that ophthalmologists should consider.
In addition to cataracts, chronic diarrhea, tendon xanthomas, and progressive neurologic deterioration are common signs of CTX, and the variability of these symptoms can often lead to a delayed diagnosis for patients.
Earlier diagnosis of CTX is a vital step toward preventing serious intellectual and physical disability, and ophthalmologists can be an important part of recognizing and diagnosing this condition.
Tools to mitigate underdiagnosis of CTX include greater disease awareness, genetic testing, newborn screening, and biochemical testing.
Chenodeoxycholic acid (CDCA) is not currently approved by the U.S. Food and Drug Administration for the treatment of CTX, but it is a mainstay of treatment for this patient population.
A phase 3 study of CDCA is underway to support a potential future FDA approval.
The randomized, placebo-controlled, double-blind RESTORE study is assessing CDCA 250 mg given 3 times daily versus placebo. A total of 14 patients have been enrolled (mean age, 39 years), and five patients (35.7%) had ophthalmologic disorders other than cataracts.
Some highlights of the outcomes include a statistically significant:
- 20-fold increase (P<.0001) in urine 23S-pentol upon CDCA withdrawal in the placebo group compared with CDCA (primary endpoint)
- 2.8-fold increase (P=.0083) in plasma cholestanol upon CDCA withdrawal in the placebo group compared with CDCA
- 12.5-fold increase (P<.0001) in plasma bile alcohol upon CDCA withdrawal in the placebo group compared with CDCA
The most common treatment-related adverse events associated with CDCA were diarrhea (n=5) and headache (n=3). One severe treatment-related adverse event (drug overdose) occurred and led to treatment discontinuation.
“The RESTORE trial further demonstrates the efficacy and safety of CDCA treatment for patients with CTX and highlights the potential for CDCA to control aberrant bile acid synthesis, prevent the toxic accumulation of cholestanol and bile alcohols, and help reduce the effects of CTX progression,” according to the presentation.
In conclusion, the presenters highlighted that:
- Distinguishing CTX from other sterol disorders is important and facilitates optimal treatment
- Laboratory testing for CTX can help overcome some diagnostic challenges
- Early diagnosis and treatment are important to prevent disease progression
Hear Dr. Schaefer talk more about early-onset cataracts and CTX.
Reference
Schaefer EJ, DeBarber AE, Duell PB. The hidden impact of sterol disorders. Differential diagnoses in CTX and other lipid disorders. Presented at the NLA 2024 Scientific Sessions, May 30-June 2, 2024, Las Vegas, Nevada.
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