Early onset cataracts, other indicators, should raise suspicion of cerebrotendinous xanthomatosis

Early onset cataracts, chronic diarrhea, and neurological deficits during childhood are crucial, when coupled with a negative family history of neurological and metabolic disorders, should raise suspicion of cerebrotendinous xanthomatosis (CTX) and prompt further investigation, according to a recently published case report.

CTX, often associated with variants in the CYP27A1 gene, causes a dysregulation in cholesterol metabolism, leading to the accumulation of specific metabolites, such as cholestanol. These metabolites have a particular affinity for neuronal tissue and tendons, resulting in a wide range of debilitating symptoms.

In a case report, 2 brothers experienced early onset cataracts, watery stools, and thoracic kyphoscoliosis. They underwent magnetic resonance imaging (MRI) scans, which revealed hyperintense alterations in their central nervous system. Intratendinous xanthomas were also observed in their Achilles tendons.

With the collected data, a biochemical analysis was conducted, indicating elevated levels of cholestanol, lathosterol, and 7-dehydrocholesterol. Their family history provided no clues to neurological or metabolic disorders, prompting the medical team to consider a genetic cause for their condition.

Genetic testing confirmed both individuals carried a pathogenic variant (c.1184+1G>A) in the CYP27A1 gene, confirming the diagnosis of CTX.

This discovery not only provided much-needed clarity to the patients and their families but also opened the door to a potentially life-changing treatment.

The patients were started on chenodeoxycholic acid (CDCA) therapy, and subsequent follow-up examinations have revealed significant improvement in their conditions.

Reference
Brlek P, Bulić L, Glavaš Weinberger D, et al. Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to CYP27A1 Gene Mutation with Chenodeoxycholic Acid Therapy. Biomedicines. 2023;11(5):1430. doi: 10.3390/biomedicines11051430. PMID: 37239101; PMCID: PMC10216236.