Neuropsychiatric Symptom Burden of Cerebrotendinous Xanthomatosis, the Importance of Diagnosing Early, and the Impact of CDCA Treatment: A US-based Survey
Biochemical/Metabolic and Therapeutics
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Introduction:
Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive metabolic disorder of bile acid synthesis resulting in a pathological storage of lipids throughout body tissues. This leads to early-onset chronic diarrhea, juvenile-onset bilateral cataracts, tendon xanthomas, and progressive neurological deterioration. These debilitating symptoms underscore the need to diagnose CTX early in order to limit serious neuropsychiatric and physical disability. There is a paucity of data in the literature focused on the burden and severity of neurologic and psychiatric symptoms associated with CTX. The aim of this survey was to provide information about the presentation, burden, and severity of neuropsychiatric symptoms in CTX from the patient perspective, along with the impact of chenodeoxycholic acid (CDCA), the current standard of care for CTX, on these symptoms and overall quality of life (QoL).
Methods:
A survey of patients with self-reported CTX (or reported by their caregiver) was conducted. The 53-question web-based survey was focused on the impact of neurologic and psychiatric symptoms in patients with CTX, how the severity of these symptoms affected QoL, and therapeutic interventions used to address these symptoms. The survey was distributed to participants via the CTX Alliance. Responses were collected from May to June 2024.
Results:
Thirty-five participants responded to this survey who were either diagnosed with CTX (29%) or were caregivers (71%) of a patient(s) with CTX. Most participants had genetic confirmation of CTX (71.4%), were male (54%), with a median age of 29 years (Q1:16, Q3:34) at the time of CTX diagnosis. Eighty percent of participants indicated that they are experiencing neurologic and/or psychiatric decline. Neurologic changes that were associated with a very high/severe burden included gait difficulty (65%), ataxia (47%), sensory changes (47%), speech changes (46%), tremors (40%), and dystonia (36%). Psychiatric changes that were associated with a very high/severe burden included learning difficulties (87%), anxiety (76%), negative behavioral changes (57%), cognitive decline (57%), ADHD (56%), aggression (50%), agitation (43%), and depression (36%). All participants with autistic symptoms characterized the burden as severe. Importantly, all of these neurologic and psychiatric symptoms occurred years before a confirmed diagnosis of CTX and the earlier these symptoms were present, the more burdensome they were. Eighty-six percent of participants were receiving CDCA treatment for CTX, with the majority taking 750mg/d (82%), and 63% were on CDCA therapy for over 6 years. Since starting CDCA these participants reported improvements in the ability to concentrate (58%), cognitive functioning (54%), and overall improvement in QoL (67%).
Conclusion:
The neurologic and psychiatric symptoms associated with CTX have a major adverse impact on QoL, and these symptoms tend to be observed years before an official diagnosis of CTX is made, underscoring the importance of early CTX diagnosis. CDCA has demonstrated a positive improvement on several neuropsychiatric symptoms associated with CTX including the ability to concentrate, cognitive functioning, and overall QoL. These data highlight the need for additional systematic research evaluating the impact of CDCA on CTX-associated neuropsychiatric symptoms.
Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive metabolic disorder of bile acid synthesis resulting in a pathological storage of lipids throughout body tissues. This leads to early-onset chronic diarrhea, juvenile-onset bilateral cataracts, tendon xanthomas, and progressive neurological deterioration. These debilitating symptoms underscore the need to diagnose CTX early in order to limit serious neuropsychiatric and physical disability. There is a paucity of data in the literature focused on the burden and severity of neurologic and psychiatric symptoms associated with CTX. The aim of this survey was to provide information about the presentation, burden, and severity of neuropsychiatric symptoms in CTX from the patient perspective, along with the impact of chenodeoxycholic acid (CDCA), the current standard of care for CTX, on these symptoms and overall quality of life (QoL).
Methods:
A survey of patients with self-reported CTX (or reported by their caregiver) was conducted. The 53-question web-based survey was focused on the impact of neurologic and psychiatric symptoms in patients with CTX, how the severity of these symptoms affected QoL, and therapeutic interventions used to address these symptoms. The survey was distributed to participants via the CTX Alliance. Responses were collected from May to June 2024.
Results:
Thirty-five participants responded to this survey who were either diagnosed with CTX (29%) or were caregivers (71%) of a patient(s) with CTX. Most participants had genetic confirmation of CTX (71.4%), were male (54%), with a median age of 29 years (Q1:16, Q3:34) at the time of CTX diagnosis. Eighty percent of participants indicated that they are experiencing neurologic and/or psychiatric decline. Neurologic changes that were associated with a very high/severe burden included gait difficulty (65%), ataxia (47%), sensory changes (47%), speech changes (46%), tremors (40%), and dystonia (36%). Psychiatric changes that were associated with a very high/severe burden included learning difficulties (87%), anxiety (76%), negative behavioral changes (57%), cognitive decline (57%), ADHD (56%), aggression (50%), agitation (43%), and depression (36%). All participants with autistic symptoms characterized the burden as severe. Importantly, all of these neurologic and psychiatric symptoms occurred years before a confirmed diagnosis of CTX and the earlier these symptoms were present, the more burdensome they were. Eighty-six percent of participants were receiving CDCA treatment for CTX, with the majority taking 750mg/d (82%), and 63% were on CDCA therapy for over 6 years. Since starting CDCA these participants reported improvements in the ability to concentrate (58%), cognitive functioning (54%), and overall improvement in QoL (67%).
Conclusion:
The neurologic and psychiatric symptoms associated with CTX have a major adverse impact on QoL, and these symptoms tend to be observed years before an official diagnosis of CTX is made, underscoring the importance of early CTX diagnosis. CDCA has demonstrated a positive improvement on several neuropsychiatric symptoms associated with CTX including the ability to concentrate, cognitive functioning, and overall QoL. These data highlight the need for additional systematic research evaluating the impact of CDCA on CTX-associated neuropsychiatric symptoms.