Cerebrotendinous Xanthomatosis (CTX): A Treatable Cause of Autism

Autism spectrum disorder is an entity that reflects a scientific consensus. Several previously separated disorders are actually a single spectrum disorder with differentlevels of symptom severity in two core domains - deficits in social communication and interaction, and restricted repetitive behaviors. Autism spectrum disorder is diagnosed in all racial, ethnic and socioeconomic groups and because of its increased prevalence, reported worldwide through the last years, made it one of the most discussed childrenpsychiatric disorders. In term of aetiology as several other complex diseases, autism spectrum disorder is considered to have a strong genetic component. Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of bile acid synthesis caused by mutations in the cytochrome P450 CYP27A1 gene that results in production of a defective sterol 27-hydroxylase enzyme. CTX is associated with abnormally high levels of cholestanol in the blood and accumulation of cholestanol and cholesterol in the brain, tendon xanthomas, and bile. Hallmark clinical manifestations of CTX include chronic diarrhea, bilateral cataracts, tendon xanthomas, and neurologic dysfunction. The clinical picture ranges from being nearly asymptomatic in early childhood, up to severe disability at adult age. Infantile-onset diarrhea and juvenileonset cataract are the earliest symptoms in childhood. Although CTX is a rare disorder, it is thought to be underdiagnosed, as presenting signs and symptoms may be nonspecific with significant overlap with other more common conditions. There is marked variability in signs and symptoms, severity, and age of onset between patients. The disease course is progressive and potentially debilitating or fatal, particularly with respect to neurologic presentations that can include intellectual disability, autism, behavioral and psychiatric problems, and dementia, among others. Treatment with chenodeoxycholic acid (CDCA; chenodiol) is the current standard of care. CDCA can help restore normal sterol, bile acid, bile alcohol, and cholestanol levels. CDCA also is generally effective in preventing adverse clinical manifestations of the disease from occurring or progressing if administered early enough. Improved screening and awareness of the condition may help facilitate early diagnosis and treatment. ASD is early and probably underestimated frequent feature in CTX. Metabolic screening for CTX should be performed in patients with ASD when accompanied by diarrhea, intellectual disability, juvenile cataract, and/or neurological involvement. Early recognition allows for earlier initiation of specific treatment and will improve clinical outcome. The behavioral problems stabilized or improved after treatment initiation with chenodeoxycholic acid (CDCA) in all pediatric patients.

کلیدواژه ها:

Autism spectrum disorder ، Cerebrotendinous xantomatosis ، Treatment