Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
Ophthalmology. 2013 May;120(5):956-60. doi: 10.1016/j.ophtha.2012.10.032. Epub 2013 Jan 31.
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.
Prospective case series.
Four siblings and their 2 parents, who are first cousins.
Ophthalmic examination, general physical examination, and exome sequencing guided by homozygosity analysis.
Ophthalmic findings, general clinical findings, and results of CYP27A1 candidate gene testing.
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.
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.
FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
脑腱性黄瘤病是一种由隐性 CYP27A1 突变引起的进行性神经退行性贮积病，其特征是包括晶状体和大脑在内的多种组织中胆甾醇和胆固醇异常沉积。口服鹅去氧胆酸具有预防作用并且具有治疗作用，但并未得到最佳应用，因为这种疾病通常诊断较晚或根本不诊断。当受影响的儿童出现晶状体混浊时，眼科医生通过识别少年性白内障表型，具有促进早期诊断和治疗的独特潜力。本研究突出了经基因确证的疾病家族中晶状体混浊的形态。
前瞻性病例系列。
4 名兄弟姐妹及其 2 位同为表亲的父母。
眼科检查、全身检查和外显子组测序，由同系分析指导。
眼科发现、一般临床发现和 CYP27A1 候选基因检测结果。
2 位姐妹在 10 岁之前均有视力症状，她们的双侧晶状体均有独特的斑点状沉积物，伴有明显的后囊白内障。当她们在 8 岁时首次检查时，她们无症状的弟弟也有相同的双侧斑点状沉积物，但后囊混浊程度较轻；1 年后，他出现了前囊混浊并出现了症状。无症状的父母虽然斑点状混浊较少，但也有明显的类似混浊，定位于或靠近前 Y 缝；而无症状的姐姐则没有。基因分析显示，3 名有症状的兄弟姐妹均为已知 CYP27A1 突变（c.1263+1G → A）的纯合子，2 位父母均为杂合子，无症状的姐姐则没有突变。当被具体询问时，3 名受影响的儿童在幼儿时期曾多次经历复发性腹泻，这是该病的常见特征。
受影响的儿童出现了不常见的斑点状晶状体沉积物模式。随着时间的推移，后囊混浊（仅后囊或后囊和前囊）发展并导致视力症状。在这种情况下，幼年晶状体的发现应引起对这种可治疗的代谢紊乱的怀疑，尤其是在幼儿时期反复发作腹泻的情况下。位于或靠近前 Y 缝处的类似斑点状的无症状混浊可能是携带者的特征。
作者无本文讨论的任何材料的专有或商业利益。
