Lenticular changes in cerebrotendinous xanthomatosis, a treatable metabolic disorder that is important to recognize

Abstract

Cerebrotendinous xanthomatosis is a progressive neurodegenerative storage disease characterized by abnormal deposition of cholestanol and cholesterol in multiple tissues, including the lens and brain, and caused by recessive CYP27A mutations. Ophthalmologists have the unique potential to facilitate earlier diagnosis and preventative treatment by recognizing the juvenile cataract phenotype. We highlight the morphology of lens opacities in a family with genetically confirmed disease. Retrospective case series. Two sisters, each visually symptomatic before 10 years of age, had a unique pattern of bilateral fleck deposits throughout the lens with significant posterior capsular cataract. When initially examined at 8 years old, their then asymptomatic younger brother had the same bilateral fleck deposits with minimal posterior capsular opacity; one year later he developed anterior capsular opacity and became symptomatic. Both asymptomatic parents had few but distinct similar flecks localized at the Y-suture while an asymptomatic sister did not. Genetic analysis revealed homozygosity for a novel CYP27A 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 had recurrent bouts of diarrhea since early childhood, which is a common feature of the disease. An usual pattern of fleck lenticular deposits were seen in affected children. With time posterior and/or anterior capsular opacity developed and caused visual symptoms. Asymptomatic fleck-like opacities at the Y-suture may be a carrier sign. Such juvenile lenticular findings should raise suspicion for this treatable metabolic disorder.