Cerebrotendinous Xanthomatosis

Clinical Characteristics
Ocular Features: 

Juvenile cataracts are the primary ocular feature of this disorder and are found in virtually all patients.  These often cause the first symptoms and become evident in the first decade and almost always by the third decade of life.  Lens opacification may require extraction at that time and aspirated lens material may contain lipid-containing vacuoles.  However, some cataracts may not be diagnosed until the 5th or 6th decades after the onset of neurological symptoms, usually because the opacities are located in the peripheral cortex and do not cause visual symptoms. 

Optic atrophy occurs in nearly half of affected individuals.  Yellowish flakes resembling cholesterol crystals can sometimes be seen in the vitreous. The fundus may have scattered hard exudates and cholesterol-like deposits along the vascular arcades and arterioles show evidence of atherosclerosis.  RPE window defects are common.

Systemic Features: 

CTX has serious systemic neurologic signs and symptoms resulting from a deficiency of a mitochondrial enzyme, sterol 27-hydroxylase.  The result is reduced bile acid synthesis and increased levels of cholestanol in plasma, tissues, and CSF.  This results in a characteristic phenotype of tendon xanthomas, and neurological dysfunction including mental regression or illness, cerebellar ataxia, peripheral neuropathy, seizures, and pyramidal signs to various degrees.  Neonatal jaundice and diarrhea are common.

Genetics

This autosomal recessive disorder results from a mutation in the CYP27A1 gene (2q33-qter) encoding sterol 27-hydroxylase.

Treatment
Treatment Options: 

This is a treatable disorder in which administration of chenodeoxycholic acid (CDCA) is beneficial.  This compound is virtually absent from bile in people with CTX.  Exogenous administration reduces high levels of cholesterol and cholestanol in the CSF, tissues, and plasma with improvement in mental function and signs of peripheral neuropathy and cerebellar dysfunction.  It is frequently given in combination with other HMG-CoA inhibitors such as pravastatin.  Early diagnosis and treatment are important.

References
Article Title: 

References

Mignarri A, Gallus GN, Dotti MT, Federico A. A suspicion index for early diagnosis and treatment of cerebrotendinous xanthomatosis. J Inherit Metab Dis. 2014 May;37(3):421-9.

PubMedID: 24442603

Keren Z, Falik-Zaccai TC. Cerebrotendinous xanthomatosis (CTX): a treatable lipid storage disease. Pediatr Endocrinol Rev. 2009 Sep;7(1):6-11. Review.

PubMedID: 19696711

Berginer VM, Gross B, Morad K, Kfir N, Morkos S, Aaref S, Falik-Zaccai TC. Chronic diarrhea and juvenile cataracts: think cerebrotendinous xanthomatosis and treat. Pediatrics. 2009 Jan;123(1):143-7.

PubMedID: 19117873

Dotti MT, Rufa A, Federico A. Cerebrotendinous xanthomatosis: heterogeneity of clinical phenotype with evidence of previously undescribed ophthalmological findings. J Inherit Metab Dis. 2001 Dec;24(7):696-706.

PubMedID: 11804206