Lenticular deposits could be early sign of cerebrotendinous xanthomatosis

This prospective study found that an usual pattern of juvenile fleck lenticular deposits occurs in cerebrotendinous xanthomatosis. This information could prove vital in helping ophthalmologists diagnose and treat the disease early.

Cerebrotendinous xanthomatosis is a lipid storage disease resulting from a defect in bile acid synthesis. It is characterized by abnormal deposition of cholestanol and cholesterol in multiple tissues such as the brain and the crystalline lens. Early childhood recurrent diarrhea and juvenile cataract are early manifestations; cognitive decline and tendon xanthomas occur progressively in the second and third decades of life.

Even though juvenile cataract is a virtually universal feature of the cerebrotendinous xanthomatosis, in most reports of the condition the morphology of lens opacities is not discussed. This study highlights the unique juvenile cataract phenotype of three affected individuals from a consanguineous family with genetically confirmed disease and documents the lens phenotype of the genetically confirmed carrier parents.

Two sisters with juvenile cataract were referred for ophthalmic evaluation. Each had a unique pattern of bilateral fleck deposits throughout the lens with significant posterior capsular cataract. When initially examined at 8 years of age, their then-asymptomatic younger brother had the same bilateral fleck deposits with minimal posterior capsular opacity. One year later, he demonstrated anterior capsular opacity and became symptomatic.

Both asymptomatic parents had few but distinct similar flecks localized at or near the anterior Y-suture, whereas an asymptomatic sister did not. Genetic analysis revealed homozygosity for a known CYP27A1 mutation in the three symptomatic siblings, heterozygosity for the mutation in the two parents, and no mutation in the asymptomatic sister. When specifically questioned, the three affected children had experienced recurrent bouts of diarrhea in early childhood, which is a common feature of the disease.

The authors conclude that ophthalmologists have the unique opportunity to facilitate earlier diagnosis and decreased morbidity by recognizing the ocular phenotype when affected children or young adults develop symptomatic cataract. Juvenile fleck lenticular opacities should raise suspicion for cerebrotendinous xanthomatosis, particularly when accompanied by posterior and/or anterior capsular opacities and especially when in the context of recurrent early childhood diarrhea.