There are three diagnostic methods for CTX.  Individuals are often diagnosed using a combination of these three methods: 1) clinical features, 2) genetic testing, and/or 3) biochemical testing.

1. Clinical features – CTX is characterized by distinct signs and symptoms, which may include among others diarrhea, cataracts, xanthomas (abnormal tendon growths), and neurologic problems that can be progressive, such as epilepsy, movement disorders, impaired speech, decreased sensation in the arms and legs, autism, dementia, and depression. Osteoporosis is another sign of CTX.

2. Genetic testing – CTX is inherited in an autosomal recessive pattern, which means disease-causing gene variants are present on both copies of the CYP27A1 gene in each cell of an affected individual. The parents of a child with an autosomal recessive condition each carry one copy of the disease-causing gene variant, but they typically do not show signs or symptoms of the condition because their one working copy of the gene is sufficient to prevent disease.

Genetic testing uses sequencing and deletion analysis of the CYP27A1 gene and can be done on either blood samples or by collection of genetic material from the saliva or cheek.

Genetic counseling is recommended for families and individuals undergoing testing. If the results of genetic testing are unclear, then biochemical testing is helpful to rule out or confirm the diagnosis.

3. Biochemical testing – Doctors test for specific molecules generated in abnormal bile acid pathway (bile alcohols) in urine and/or blood (cholestanol, bile alcohols and bile acid precursors).