Psychiatric manifestations in cerebrotendinous xanthomatosis

Abstract

Cerebrotendinous xanthomatosis (CTX) is a rare and severe, but treatable, inborn disorder of bile acid biosynthesis and sterol storage with autosomal recessive inheritance and variable clinical presentation. CTX treatment consists of chenodeoxycholic acid and must be started as early as possible to prevent permanent disability. Psychiatric manifestations are rare and non-specific, and often lead to significant diagnostic and treatment delay. Therefore, better recognition of the gamut of psychiatric manifestations in CTX can diminish the risk of misdiagnosis and irreversible neurological deterioration. We hereby describe the psychiatric features in CTX. A complete review of all published cases of CTX in the medical literature was undertaken and the case reports with psychiatric presentation were collected and analyzed. We also describe the psychiatric features in relation to the neurological semeiology in six patients with CTX diagnosed at the La Salpêtrière Hospital. We conclude that psychiatric manifestations in CTX follow a bimodal/bitemporal pattern, appearing early in the disease course in the form of a behavioral/personality disorder associated with learning difficulties or mental retardation, or manifesting in advanced disease in the setting of dementia as rich neuropsychiatric syndromes, such as frontal, orbitofrontal or frontotemporal syndromes of cortico-subcortical dementia encompassing behavioral/personality disturbance, affective/mood disorders or psychotic disorders. Behavioral/personality disturbance in childhood or adolescence, especially when accompanied by learning difficulties, should therefore lead to further investigation to exclude CTX, as early diagnosis and treatment is critical for prognosis.

Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX)

“…2 (Mignarri et al 2014;Fraidakis 2013;Berginer et al 1993;Berginer and Abeliovich 1981;Verrips et al 1999a;Waterreus et al 1987;Verrips et al 2000a;Berginer et al 1994)). Clinical hallmarks include premature bilateral cataracts (88% of patients based on a review of selected international case series), intractable diarrhea (~50%), progressive neurologic signs and symptoms (pyramidal, 77%; cerebellar, 62%), and tendon xanthomas (69%) (Verrips et al 2000c;Mignarri et al 2014).…”

“…Symptoms reflecting neurologic dysfunction, such as intellectual disability and gait disturbances, are common presenting symptoms (Pilo-de-la-Fuente et al 2011). Neurologic manifestations generally emerge during adolescence or early adulthood and worsen over time (Moghadasian 2004); however, developmental delays, intellectual disability, cognitive impairment, and learning difficulties may emerge during childhood (Lorincz et al 2005;Larson et al 2017;Degos et al 2016;Fraidakis 2013). As the disease progresses, intellectual function continues to deteriorate and frank dementia may be present (Lorincz et al 2005;Berginer et al 2015).…”

“…As the disease progresses, intellectual function continues to deteriorate and frank dementia may be present (Lorincz et al 2005;Berginer et al 2015). Psychiatric manifestations may appear during childhood or adolescence in the form of behavioral/personality disorders, sometimes presenting as autism, and may be associated with learning difficulties (Fraidakis 2013;Ly et al 2014;Stelten et al 2017). Attentional deficits, including attention deficit hyperactivity disorder (ADHD), may be presenting symptoms in young children (Fraidakis 2013;Ly et al 2014).…”

“…Psychiatric manifestations may appear during childhood or adolescence in the form of behavioral/personality disorders, sometimes presenting as autism, and may be associated with learning difficulties (Fraidakis 2013;Ly et al 2014;Stelten et al 2017). Attentional deficits, including attention deficit hyperactivity disorder (ADHD), may be presenting symptoms in young children (Fraidakis 2013;Ly et al 2014). Alternatively, psychiatric disorders can emerge in advanced disease in older patients, often in the context of dementia, presenting as neuropsychiatric syndromes (Fraidakis 2013).…”

“…Attentional deficits, including attention deficit hyperactivity disorder (ADHD), may be presenting symptoms in young children (Fraidakis 2013;Ly et al 2014). Alternatively, psychiatric disorders can emerge in advanced disease in older patients, often in the context of dementia, presenting as neuropsychiatric syndromes (Fraidakis 2013). Epileptic seizures may occur during childhood (Berginer et al 2015); infantile spasms have also been reported, but only rarely (Larson et al 2017).…”