Cerebrotendinous xanthomatosis is an autosomal recessive disease that often begins in childhood but frequently diagnosed only in adulthood.
Summary
Cause
Cerebrotendinous xanthomatosis (CTX, OMIM #213700) is an autosomal recessive disorder. CTX is associated with elevated production of cholestanol, which accumulates in various tissues, and increased levels of bile alcohols in the urine.
Cholestanol accumulation is neurotoxic, particularly to Purkinje cells. The diagnosis of CTX is based on the measurement of plasma cholestanol levels and is confirmed by identifying two pathogenic mutations in the CYP27A1 gene.
Symptoms
Patients with CTX typically present with a combination of neuropsychiatric and extra-neurological symptoms such as infantile cholestasis or liver dysfunction, cataracts, Achilles tendon xanthomas, chronic diarrhea, osteoporosis, premature arteriosclerosis, and cardiovascular diseases.
Neurological symptoms can include learning difficulties and/or autism spectrum disorders, spastic paraplegia, cerebellar ataxia, peripheral neuropathy, bulbar involvement, epilepsy, parkinsonism, dementia, and/or psychiatric disorders.
Treatment
Chenodeoxycholic acid (CDCA) remains the treatment of choice for CTX, as it is the only medication that has consistently shown beneficial effects on neurological symptoms. Exogenous CDCA acts through negative feedback inhibition on the endogenous synthesis of bile acids and cholestanol.
CDCA significantly reduces plasma cholestanol levels in patients and prevents its accumulation in tissues. The response to treatment is strongly dependent on the timing of CDCA initiation.