title: Juvenile cataract morphology in 3 siblings not yet diagnosed with cerebrotendinous xanthomatosis.
abstract: OBJECTIVE
  Cerebrotendinous xanthomatosis is a progressive neurodegenerative storage disease caused by recessive CYP27A1 mutations and is characterized by abnormal deposition of cholestanol and cholesterol in multiple tissues, including the lens and brain. Oral chenodeoxycholic acid is preventive and can be therapeutic, but is not used optimally because the condition typically is diagnosed late or not at all. When affected children demonstrate lens opacities, ophthalmologists have the unique potential to facilitate earlier diagnosis and treatment by recognizing the juvenile cataract phenotype. This study highlights the morphology of lens opacities in a family with genetically confirmed disease.
  
  
  METHODS
  Prospective case series.
  
  
  METHODS
  Four siblings and their 2 parents, who are first cousins.
  
  
  METHODS
  Ophthalmic examination, general physical examination, and exome sequencing guided by homozygosity analysis.
  
  
  METHODS
  Ophthalmic findings, general clinical findings, and results of CYP27A1 candidate gene testing.
  
  
  RESULTS
  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 of age, their then-asymptomatic younger brother had the same bilateral fleck deposits with minimal posterior capsular opacity; 1 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 (c.1263+1G → A) in the 3 symptomatic siblings, heterozygosity for the mutation in the 2 parents, and no mutation in the asymptomatic sister. When specifically questioned, the 3 affected children had experienced recurrent bouts of diarrhea in early childhood, which is a common feature of the disease.
  
  
  CONCLUSIONS
  An unusual pattern of fleck lenticular deposits was seen in affected children. With time, capsular opacities (posterior only or posterior and anterior) developed and caused visual symptoms. Such juvenile lenticular findings should raise suspicion for this treatable metabolic disorder, especially when in the context of recurrent diarrhea during early childhood. Asymptomatic fleck-like opacities at or near the anterior Y-suture may be a carrier sign.
  
  
  BACKGROUND
  The author(s) have no proprietary or commercial interest in any materials discussed in this article.
authors: Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. arif.khan@mssm.edu
authors: Arif O
authors: AO
authors: Khan
authors: Mohammed A
authors: MA
authors: Aldahmesh
authors: Jawaher Y
authors: JY
authors: Mohamed
authors: Fowzan S
authors: FS
authors: Alkuraya
mesh_terms: D000293:Adolescent; D002648:Child; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics*; D003241:Consanguinity; D003318:Corneal Opacity / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D014792:Visual Acuity / Q000502:physiology; D019294:Xanthomatosis, Cerebrotendinous / Q000235:genetics / Q000473:pathology*; D055815:Young Adult; D038203:alpha-Crystallin B Chain / Q000235:genetics
chemical_list: C059215:CRYAB protein, human; D038203:alpha-Crystallin B Chain; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase