Prevalence of Cerebrotendinous Xanthomatosis Among Patients Diagnosed With Acquired Juvenile-Onset Idiopathic Bilateral Cataracts
Monte A. Del Monte, MD; Sharon F. Freedman, MD; Charlotte Brennand, MPH; P. Barton Duell, MD; John Fiorito, PharmD, MBA; Allison Loh, MD; Randall Marshall, MD
K. Kellogg Eye Center, University of Michigan
Ann Arbor, Michigan, USA
Introduction: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive bile acid synthesis disorder caused by mutations in CYP27A1, the gene encoding sterol 27-hydroxylase, which leads to elevated plasma cholestanol and urinary bile alcohols. Symptoms may include early-onset chronic diarrhea, juvenile-onset cataracts, cholestatic jaundice, tendon xanthomas, and progressive neurological deterioration. Diagnosis often occurs after onset of permanent damage. Strategies for early diagnosis are needed.
Methods: Observational, multicenter study to evaluate the prevalence of CTX among patients with idiopathic bilateral cataracts diagnosed between ages 2-21 years. Plasma cholestanol levels >/=0.4 mg/dL or positive urine bile alcohols measured by GC/MS prompted CYP27A1 genetic testing.
Results: Of 170 tested patients, 3 (1.8%) had biochemical (elevated plasma cholestanol: (>1.6mg/dL, 3.17mg/dL, >3.2mg/dL), and positive urine bile alcohols) and as well as genetic confirmation of newly-diagnosed CTX. Mean age at cataract surgery was 12.7 years (range 8-18). Reported symptoms included abnormal gait/balance (n=3), learning disability/developmental delay (n=2), seizures (n=2), frequent fractures (n=2), and chronic diarrhea (n=1).
Discussion: To date, 1.8% of patients in this study had CTX, which is 500-1000 times the currently estimated prevalence. A fourth patient was screened and tested positive prior to the initiation of the site. These data suggest that juvenile-onset idiopathic bilateral cataracts may be a marker for CTX that can facilitate early identification of CTX, possibly allowing prevention of permanent neurological damage.
Conclusion: Ophthalmologists can play an important role in helping to diagnose CTX earlier, possibly preventing irreversible neurological decline and other serious complications.
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3. Lorincz MT, et al. Cerebrotendinous xanthomatosis: possible higher prevalence than previously recognized. Arch Neurol. 2005; 62(9): 1459-63.