CTX can lead to serious neurologic problems

Untreated CTX may lead to progressive neurologic problems

Patients with advanced CTX show evidence of lipid deposits and loss of white matter in many areas of the brain.^1,2

Patients with CTX whose diagnosis is missed or delayed may face severe intellectual and physical disability in their early adult years^3,4

In CTX, early signs of intellectual disability usually present when patients are of school age.³ Intellectual disability may progress to dementia when patients are in their twenties and thirties.^1,4 Physically disabling cerebellar and pyramidal neurologic signs also often develop, usually in the third decade of life.^3,5

By the time of diagnosis (mean age: 35.5 ± 11.8 years³), pyramidal and cerebellar signs are present in approximately 60% to 70% of patients.^3,4 Intellectual disability is apparent in well over 50% of patients at this stage.^3,4

Early neurologic signs and symptoms of CTX can be subtle and easily mistaken for other problems^3,4,6,7

Due to the progressive nature of CTX, it can take time for neurological problems to become apparent. Early developmental milestones may be achieved punctually, but patients then begin to fall behind.³ Patients may exhibit poor school performance, learning difficulties, sustained infantile behavior, and lack of age-appropriate self-care skills.³ In case reports of patients with CTX, patients had received childhood diagnoses of learning disorders, behavioral difficulties, attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, etc.^3,6,7

Seizures are also common in patients with CTX³

Epilepsy was present in 24% to 33% of patients at the time of diagnosis, with variable age of onset.^3,4 Some cases describe febrile seizures that persist beyond infancy into childhood.⁸

Without early diagnosis and appropriate management, CTX can progress to serious physical and intellectual disability^3,4

Physically disabling neurologic dysfunction, including pyramidal paresis, cerebellar ataxia, and peripheral neuropathy, develops and progresses with increasing age in a majority of patients with CTX.^3,5 Spastic paraparesis and ataxia occurred in 77% and 62% of cases, respectively, usually at the end of the third decade.³

In advanced cases, intellectual disability may progress to cortical/subcortical dementia from the third decade of life onwards.^1,4

Parkinsonism is a rarer late manifestation of CTX that may occur in approximately 10% of patients.^1,3 Psychiatric disturbances have also been described in CTX case reports.¹ In a case review of 425 published cases of CTX, the incidence of psychiatric disturbances was 13%.¹