{ "@context": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/context/doc", "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084", "id": "CG-AC:AC1084", "type": "ClinicalActionabilityReport", "metadata": { "schemaLabel": "AC-Sepio.Beta-1 (Unofficial)", "contentVersionId": "30691", "producedAtUTC": "Thu, 10 Sep 2026 19:40:01 -0000", "note": "DISCLAIMER: The SEPIO-inspired schema presented here is an initial prototype for Clinical Actionability curation summaries and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema." }, "description": "JSON-LD representation of ClinGen Actionability Stage 2 report modeled with SEPIO. The hierarchically structured document will include:\n1. Contextual & topic information, such as the **conditions/diseases** and the **genes**.\n2. Categorized **evidence narratives**, with references.\n\t* This content corresponds to the texts within the *Actionability Summary Report*\n4. **Outcome & Intervention** pairs, with **consensus scoring** in 5 dimensions:\n\t1. Outcome Severity\n\t2. Outcome Likelihood\n\t3. Intervention Effectiveness\n\t4. Nature of the Intervention\n\t5. Total (Overall) Score\n\n*( Note: The summary report does not include the **Screening Survey** which led to preparation of the actionability report. )", "condition": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/co", "id": "CG-AC:AC1084/co", "type": "GeneticCondition", "label": "Cerebrotendinous xanthomatosis" }, "outcome": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/ou/Morbidity%20and%20mortality%20resulting%20from%20progressive%20lipid%20accumulation", "id": "CG-AC:AC1084/ou/Morbidity and mortality resulting from progressive lipid accumulation", "type": "Outcome", "label": "Morbidity and mortality resulting from progressive lipid accumulation" } ], "intervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/intv/Referral%20to%20specialist%20for%20treatment%20including%20bile%20acids", "id": "CG-AC:AC1084/intv/Referral to specialist for treatment including bile acids", "type": "Intervention", "label": "Referral to specialist for treatment including bile acids" } ], "clinicalActionabilityProfile": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/cap", "id": "CG-AC:AC1084/cap", "type": "Assertion", "assertionMethod": "The ClinGen AWG developed a standardized protocol to generate evidence-based profiles of clinical actionability of genes and associated disorders in the form of summary reports and semiquantitative metric (SQM) scores.", "releaseDate": "Thu, 18 Dec 2025 00:00:00 -0000", "releaseNum": "1.0.0", "media": "call" }, "evidenceStatements": { "evidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/en/nh", "id": "CG-AC:AC1084/en/nh", "type": "EvidenceNarrative", "narrative": "CTX is a chronic, progressive disorder. The mean age of diagnosis of CTX has been reported as around 35–37 years, by which time there is often significant neurological involvement. \\n\\nPyramidal signs (i.e., spasticity) and/or cerebellar signs almost invariably become evident between ages 20 and 30 years. Intellectual disability or dementia occurs in the third decade in more than 50% of individuals. Extrapyramidal manifestations are considered late disease manifestations, with parkinsonism being most frequently observed, followed by dystonia, myoclonus, and postural tremor. Mean age of onset of movement disorder is 40 +/- 12 years (median 40, range 13-62) years. \\n\\nSome individuals present with a spinal form of CTX, mainly characterized by myelopathy and spastic paraparesis; intellect is almost always normal.\\n\\nIf left untreated, people with CTX experience poorer prognosis, progressive, irreversible neurological damage and reduced life expectancy. In untreated people, life expectancy is 50 to 60 years. Some early deaths in infancy have also been reported due to fatal cholestasis.", "evidenceDomainTag": "Nature of the Threat.Natural History", "publication": [ "CG-AC:RF003996", "CG-AC:RF003997", "CG-AC:RF003998", "CG-AC:RF004001", "CG-AC:RF003955" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/en/cf", "id": "CG-AC:AC1084/en/cf", "type": "EvidenceNarrative", "narrative": "CTX is a lipid storage disease characterized by infantile-onset diarrhea, childhood-onset cataract, adolescent- to young adult-onset tendon xanthomas, and adult-onset progressive neurologic dysfunction (dementia, psychiatric disturbances, pyramidal and/or cerebellar signs, dystonia, atypical parkinsonism, peripheral neuropathy, and seizures). Chronic diarrhea from infancy and/or neonatal cholestasis may be the earliest clinical manifestation. CTX can cause liver disease in babies, but it is usually self-limiting. In approximately 75% of affected individuals, cataracts are the first finding, often appearing in the first decade of life. Xanthomas appear in the second or third decade; they occur on the Achilles tendon, the extensor tendons of the elbow and hand, the patellar tendon, and the neck tendons. Xanthomas have been reported in the lung, bones, and central nervous system. Some individuals show cognitive impairment/psychiatric symptoms from early infancy, whereas the majority have normal or only slightly impaired intellectual function until puberty; dementia with slow deterioration in intellectual abilities often occurs in the third decade. Neuropsychiatric symptoms such as behavioral changes, hallucinations, agitation, aggression, depression, and suicide attempts may be prominent. Coronary heart disease is also common.", "evidenceDomainTag": "Nature of the Threat.Clinical Features", "publication": [ "CG-AC:RF003996", "CG-AC:RF003997", "CG-AC:RF003998", "CG-AC:RF004000", "CG-AC:RF004001", "CG-AC:RF004002", "CG-AC:RF003955", "CG-AC:RF004007" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/en/potgd", "id": "CG-AC:AC1084/en/potgd", "type": "EvidenceNarrative", "narrative": "More than 400 individuals with cerebrotendinous xanthomatosis (CTX) have been reported. Prevalence is estimated to be approximately 3-5/100,000 worldwide. \\n\\nAmong large study groups of individuals with juvenile-onset cataracts, CTX was diagnosed in up to 1.88% of individuals.", "evidenceDomainTag": "Nature of the Threat.Prevalence of the Genetic Disorder", "publication": [ "CG-AC:RF003995", "CG-AC:RF003996", "CG-AC:RF003997", "CG-AC:RF003998", "CG-AC:RF004000" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/en/ACMI2874", "id": "CG-AC:AC1084/en/ACMI2874", "type": "EvidenceNarrative", "narrative": "Autosomal Recessive", "evidenceDomainTag": "Threat Materialization Chances.Modes of Inheritance", "publication": [ "CG-AC:RF003996", "CG-AC:RF003997", "CG-AC:RF003955" ] } ], "tieredEvidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/ten/CDEC3153", "id": "CG-AC:AC1084/ten/CDEC3153", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "5", "narrative": "A review that included 296 individuals with CTX found a mean diagnostic delay of 17 years ± 13.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF003995" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/ten/CDEC3154", "id": "CG-AC:AC1084/ten/CDEC3154", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "The mean age of diagnosis of CTX has been reported as around 35–37 years, by which time there is often significant neurological involvement.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF004001" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/ten/NOI3069", "id": "CG-AC:AC1084/ten/NOI3069", "type": "TieredEvidenceNarrative", "narrative": "CDCA is a lifelong treatment for CTX. Children and adults typically take 3 divided doses daily. \\n\\nThe adverse effects of CDCA are generally mild-to-moderate in severity, transitory and do not interfere with the therapy. In a retrospective study of 35 individuals, only 3 treatment-related adverse events were seen. These were constipation in 2 people and toxic hepatitis in 1 person, which were not considered to be serious. No treatment-related adverse events were seen in another retrospective study of 28 individuals, and treatment was reported to be ‘well tolerated’ in a study that included 14 individuals. A recent study (n=86 people with genetically confirmed CTX) found that the only treatment-related adverse event was a mild, transient increase in transaminases, which was observed in 7% of patients at baseline. In the cases that required intervention, enzyme levels normalized after dose adjustment and the original CDCA dose could be resumed. \\n\\nResults from the studies showed that the adverse effects of cholic acid (for inborn errors of primary bile acid synthesis, not specific to only CTX), were generally mild-to-moderate in severity, did not interfere with the therapy, and resolved after reducing the dose.", "evidenceDomainTag": "Acceptability of Intervention.Natures of Intervention", "publication": [ "CG-AC:RF004000", "CG-AC:RF004001", "CG-AC:RF004002", "CG-AC:RF004006" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/ten/ACPE4708", "id": "CG-AC:AC1084/ten/ACPE4708", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "5", "narrative": "A review identified 568 individuals with CTX in the literature, 392 genetically confirmed. Mean age at diagnosis was 32 years ± 15 years. The following symptoms were reported:\\n-Tendon xanthomas: 68%\\n-Bilateral cataract: 75%\\n-Chronic diarrhea: 51%\\n-Ataxia and/or spastic paraparesis: 69%\\n-Epilepsy: 18%\\n-Parkinsonism: 10%\\n-Polyneuropathy: 48%\\n-Intellectual disability/early dementia: 72%\\n-Behavioral changes/psychiatric symptoms: 45%", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF003995" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/ten/ACPE4707", "id": "CG-AC:AC1084/ten/ACPE4707", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "In a cohort of 55 individuals with CTX (age at diagnosis 35 ± 12 years) the following symptoms were observed: \\n-Chronic diarrhea: 40%\\n-Cataract: 89%\\n-Tendon xanthomas: 78%\\n-Intellectual disability: 60%\\n-Psychiatric disturbances: 44%\\n-Epilepsy: 33%\\n-Cerebellar signs: 36%\\n-Pyramidal signs: 64%\\n-Parkinsonism: 9%\\n-Polyneuropathy (EMG): 70%\\n-Cardiovascular findings: 35%\\n-Osteoporosis: 67%.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF003997" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/ten/EN3176", "id": "CG-AC:AC1084/ten/EN3176", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "No genotype-phenotype correlations for CYP27A1 have been identified.", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF003997" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/ten/EN3178", "id": "CG-AC:AC1084/ten/EN3178", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "The type, onset and severity of symptoms and progression of CTX vary considerably from one person to another, even in twins with the same pathogenic variant.", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF003998", "CG-AC:RF004000" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/ten/EN3177", "id": "CG-AC:AC1084/ten/EN3177", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "Intrafamilial variability is considerable.", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF003997" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/ten/RR2803", "id": "CG-AC:AC1084/ten/RR2803", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "Not provided", "evidenceDomainTag": "Threat Materialization Chances.Relative Risks" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/ten/PGM3087", "id": "CG-AC:AC1084/ten/PGM3087", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "Carrier frequency has been estimated to be as high as 1 in 108 to 1 in 300 in certain populations.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF003955" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/ten/PGM3086", "id": "CG-AC:AC1084/ten/PGM3086", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "Approximately 99% of probands have pathogenic variants in the CYP27A1 gene that are detectable by sequence analysis, while large deletions or duplications are rare.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF003997" ] } ], "tieredRecommendations": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/tr/ACCA3844", "id": "CG-AC:AC1084/tr/ACCA3844", "type": "TieredRecommendation", "evidenceSourceTier": "3", "recommendation": "Caution in the use of statins has been suggested.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF003997" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/tr/ACCA3843", "id": "CG-AC:AC1084/tr/ACCA3843", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "When performing anesthesia, it would be prudent to avoid succinylcholine in the presence of neuromuscular involvement associated with CTX.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF004007" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/tr/ACPM7031", "id": "CG-AC:AC1084/tr/ACPM7031", "type": "TieredRecommendation", "evidenceSourceTier": "1", "recommendation": "A systematic review assessed the use of cholic acid for treating inborn errors of primary bile acid synthesis; evidence primarily came from 4 small prospective observational studies, with some studies including people with bile acid synthesis defects due to peroxisomal disorders in addition to people with single enzyme deficiencies (n=112 total, n=9 with CTX). The studies suggest that replacement therapy with cholic acid may improve growth and clinical features associated with the given condition", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004002" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/tr/ACPM7030", "id": "CG-AC:AC1084/tr/ACPM7030", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "The following providers are important at the time of diagnosis for people (pediatric and adult) with CTX: \\n-Neurologist\\n-Metabolic specialist\\n-Geneticist\\n-Ophthalmologist.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003998" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/tr/ACSU4147", "id": "CG-AC:AC1084/tr/ACSU4147", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Annual surveillance for individuals with CTX includes: \\n-Echocardiogram\\n-Bone density evaluation.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF003997" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/tr/ACSU4146", "id": "CG-AC:AC1084/tr/ACSU4146", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "A specialist CTX center should be visited once per year. Individuals with CTX should be followed by neurology, ophthalmology and a metabolic specialist. The following tests are recommended 1-2 times/year for pediatric and adult patients: \\n-Cholestanol plasma concentration\\n-Liver function tests\\n-Neurologic (and if necessary neuropsychiatric evaluation)", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF003998" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/tr/ACPM7029", "id": "CG-AC:AC1084/tr/ACPM7029", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Considerations for anesthesia in patients with CTX include: \\n-Check aPPT and PT at time of diagnosis (prolonged coagulation times due to vitamin K deficiency); this may resolve after initiation of CDCA treatment. \\n-Take extra precautions during positioning and transport, as there is high incidence of osteopenia and osteoporosis in patients with CTX.\\n-Specifically monitor neuromuscular blockade.\\n-Possible complications include: difficult airway, hyperkalemia in patients with motor neuropathy or paresis, aspiration risk in patients with bulbar palsy. \\n-Regional including neuraxial anesthesia avoids airway issues, though possibility of neurological symptoms (esp with autonomic neuropathy) must be kept in mind.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004007" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/tr/ACPM7027", "id": "CG-AC:AC1084/tr/ACPM7027", "type": "TieredRecommendation", "evidenceSourceTier": "5", "recommendation": "A case series reviewed 19 pregnancies in females with CTX. In 11 pregnancies where mothers continued CDCA treatment, no complications were reported, and newborns were born at or near full term, with normal birth weight and Apgar scores. In 8 pregnancies where mothers did not receive CDCA, 2 newborns experienced elevated bilirubin soon after birth. One woman who stopped treatment during her pregnancy deteriorated neurologically while off treatment.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004008" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/tr/ACPM7023", "id": "CG-AC:AC1084/tr/ACPM7023", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Treatment with CDCA should not be interrupted during pregnancy.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003997" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/tr/ACPM7024", "id": "CG-AC:AC1084/tr/ACPM7024", "type": "TieredRecommendation", "evidenceSourceTier": "5", "recommendation": "A recent retrospective study evaluated the long-term effects of CDCA treatment in 86 genetically confirmed people with CTX (from 61 families) receiving CDCA for ≥6 months. Mean symptom onset was 9 ± 9 years, and mean age of diagnosis was 27 years ± 14 years. Most people (63%) were diagnosed in adulthood. Mean follow-up time was 4.78 ± 3.25 years. People diagnosed before age 28 years showed 100% neurological stabilization or improvement, whereas people diagnosed later had a higher rate of disease progression (p<0.05). CDCA effectively stabilized or improved pyramidal and cerebellar symptoms, although myoclonus and parkinsonism remained less responsive. Psychiatric symptoms showed a lower treatment response, with psychosis being the most refractory finding. Longer diagnostic delay and presence of anxiety and pyramidal/cerebellar symptoms were associated with poorer outcomes.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004006" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/tr/ACPM7026", "id": "CG-AC:AC1084/tr/ACPM7026", "type": "TieredRecommendation", "evidenceSourceTier": "1", "recommendation": "A systematic review assessed the use of CDCA for treating CTX; evidence primarily consisted of 2 small retrospective cohort studies (n=35 and n=28) and one smaller study (n=14), and a literature review that included 204 individuals. Neurological disability and dependence were measured using 2 scales in the 2 larger studies. In the main study, scores on both scales remained stable or improved between baseline and the most recent clinical current visit in about 80% of people. In the supportive study, scores remained stable in about 50-60% of people depending on the scale used. Generally, signs and symptoms of CTX resolved, improved or remained stable (not defined) in most people over the course of the main study. In the supportive study, signs and symptoms of the disease remained stable in most people, although fewer people saw positive outcomes than in the main study and some deteriorated. The poorer outcomes in the supportive study may be because people in this study were, on average, older and had higher disability scores at baseline. In the literature review, more than 70% of people experienced stabilization or improvement in clinical outcomes. In summary, the studies suggest that replacement therapy with CDCA may improve or, more often, stabilize symptoms of CTX, particularly in younger people with lower disability scores. It is likely that the clinical effects of CDCA may be overestimated because multiple therapies (dietary, pharmaceutical and supportive) are used in people with CTX.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004000" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/tr/ACPM7028", "id": "CG-AC:AC1084/tr/ACPM7028", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Once CTX is diagnosed, lifelong treatment with chenodeoxycholic acid (CDCA) is recommended as the first line treatment. While the preferred treatment is CDCA alone, CDCA can be given in combination with HMG-CoA reductase inhibitor and cholic acid is available as a second line treatment if CDCA is no longer tolerated or effective. Treatment decisions must be initiated, and monitored, by physicians experienced in the management of CTX. There have been no prospective, controlled clinical studies of CDCA or cholic acid in CTX and the rarity of the condition makes higher quality studies difficult. CTX has been treated with CDCA for over 40 years, with objectively measurable significant improvements in metabolic and clinical parameters. Treatment with CDCA and cholic acid can stop disease progression, or even sometimes prevent symptoms from occurring if they have not already developed. Evidence suggests earlier treatment allows the opportunity to stop progression sooner, leading to better outcomes.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003998", "CG-AC:RF004000", "CG-AC:RF004001", "CG-AC:RF004002", "CG-AC:RF004004", "CG-AC:RF004005" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/tr/ACPM7025", "id": "CG-AC:AC1084/tr/ACPM7025", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Recommended evaluations following the initial diagnosis of CTX (if not performed as part of the evaluation that led to the diagnosis) include: \\n-EMC and NCV studies to establish baseline\\n-Cardiac evaluation including EKG and echocardiogram\\n-Bone density study\\n-Ophthalmologic evaluation\\n-Baseline neurologic and neuropsychiatric evaluation\\n-Genetic counseling by genetics professional\\n-Assess need for family resources including community or online resources, social work involvement for parent support, home nursing referral.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003997" ] } ] }, "evidenceCategory": { "outcomeEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/oei", "id": "CG-AC:AC1084/oei", "type": "EvidenceItem", "natureOfTheThreat": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/oei/nott", "id": "CG-AC:AC1084/oei/nott", "type": "EvidenceLine", "prevalenceOfTheGeneticDisorder": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/oei/pgd", "id": "CG-AC:AC1084/oei/pgd", "type": "EvidenceItem", "keyText": "1-2 in 50000", "sourceOfPopulation": "General population", "evidenceNarrative": { "@id": "CG-AC:AC1084/en/potgd" } }, "clinicalFeatures": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/oei/cf", "id": "CG-AC:AC1084/oei/cf", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC1084/en/cf" } }, "naturalHistory": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/oei/nh", "id": "CG-AC:AC1084/oei/nh", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC1084/en/nh" } } }, "threatMaterializationChances": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/oei/tmc", "id": "CG-AC:AC1084/oei/tmc", "type": "EvidenceLine", "modeOfInheritance": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/oei/moi", "id": "CG-AC:AC1084/oei/moi", "type": "EvidenceItem", "keyText": "Autosomal Recessive", "evidenceNarrative": { "@id": "CG-AC:AC1084/en/ACMI2874" } }, "prevalenceOfTheGeneticMutation": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/oei/pgm", "id": "CG-AC:AC1084/oei/pgm", "type": "EvidenceItem", "keyText": "1-2 in 500", "sourceOfPopulation": "General population", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1084/ten/PGM3087" } }, "penetrance": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/oei/pe/ACPE4707", "id": "CG-AC:AC1084/oei/pe/ACPE4707", "type": "EvidenceItem", "keyText": ">= 40 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1084/ten/ACPE4707" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/oei/pe/ACPE4708", "id": "CG-AC:AC1084/oei/pe/ACPE4708", "type": "EvidenceItem", "keyText": ">= 40 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1084/ten/ACPE4708" } } ], "relativeRisk": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/oei/rr/RR2803", "id": "CG-AC:AC1084/oei/rr/RR2803", "type": "EvidenceItem", "keyText": "Unknown", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1084/ten/RR2803" } } ], "expressivity": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/oei/ex/EN3177", "id": "CG-AC:AC1084/oei/ex/EN3177", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1084/ten/EN3177" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/oei/ex/EN3178", "id": "CG-AC:AC1084/oei/ex/EN3178", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1084/ten/EN3178" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/oei/ex/EN3176", "id": "CG-AC:AC1084/oei/ex/EN3176", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1084/ten/EN3176" } } ] } }, "interventionEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei", "id": "CG-AC:AC1084/iei", "type": "EvidenceItem", "acceptabilityOfIntervention": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/aoi", "id": "CG-AC:AC1084/iei/aoi", "type": "EvidenceLine", "natureOfIntervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/noi/NOI3069", "id": "CG-AC:AC1084/iei/noi/NOI3069", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1084/ten/NOI3069" } } ] }, "effectivenessOfIntervention": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/eoi", "id": "CG-AC:AC1084/iei/eoi", "type": "EvidenceLine", "patientManagement": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/pm/ACPM7025", "id": "CG-AC:AC1084/iei/pm/ACPM7025", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1084/tr/ACPM7025" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/pm/ACPM7030", "id": "CG-AC:AC1084/iei/pm/ACPM7030", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1084/tr/ACPM7030" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/pm/ACPM7028", "id": "CG-AC:AC1084/iei/pm/ACPM7028", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1084/tr/ACPM7028" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/pm/ACPM7026", "id": "CG-AC:AC1084/iei/pm/ACPM7026", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1084/tr/ACPM7026" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/pm/ACPM7024", "id": "CG-AC:AC1084/iei/pm/ACPM7024", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1084/tr/ACPM7024" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/pm/ACPM7031", "id": "CG-AC:AC1084/iei/pm/ACPM7031", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1084/tr/ACPM7031" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/pm/ACPM7023", "id": "CG-AC:AC1084/iei/pm/ACPM7023", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1084/tr/ACPM7023" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/pm/ACPM7027", "id": "CG-AC:AC1084/iei/pm/ACPM7027", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1084/tr/ACPM7027" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/pm/ACPM7029", "id": "CG-AC:AC1084/iei/pm/ACPM7029", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1084/tr/ACPM7029" } } ], "circumstanceToAvoid": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/cta/ACCA3843", "id": "CG-AC:AC1084/iei/cta/ACCA3843", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1084/tr/ACCA3843" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/cta/ACCA3844", "id": "CG-AC:AC1084/iei/cta/ACCA3844", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1084/tr/ACCA3844" } } ], "surveillance": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/su/ACSU4146", "id": "CG-AC:AC1084/iei/su/ACSU4146", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1084/tr/ACSU4146" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/su/ACSU4147", "id": "CG-AC:AC1084/iei/su/ACSU4147", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1084/tr/ACSU4147" } } ] }, "conditionEscapeDetection": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/ced", "id": "CG-AC:AC1084/iei/ced", "type": "EvidenceLine", "chanceToEscapeDetection": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/cted/CDEC3154", "id": "CG-AC:AC1084/iei/cted/CDEC3154", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1084/ten/CDEC3154" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1084/iei/cted/CDEC3153", "id": "CG-AC:AC1084/iei/cted/CDEC3153", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1084/ten/CDEC3153" } } ] } } }, "references": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003955", "id": "CG-AC:RF003955", "type": "Publication", "publicationType": "OMIM", "citation": "Online Medelian Inheritance in Man, OMIM. Johns Hopkins University, Baltimore, MD. Cerebrotendinous xanthomatosis; ctx. MIM: 2137002025 Jun 03. ", "webUrl": "https://www.omim.org/entry/213700", "xdbref": [ "OMIM:213700" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003995", "id": "CG-AC:RF003995", "type": "Publication", "publicationType": "PMID", "citation": "Badura-Stronka M, Hirschfeld AS, Winczewska-Wiktor A, Budzyńska E, Jakubiuk-Tomaszuk A, Piontek A, Steinborn B, Kozubski W. First case series of Polish patients with cerebrotendinous xanthomatosis and systematic review of cases from the 21st century. Clin Genet. (2022) 101(1399-0004):190-207.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=34689324", "xdbref": [ "PMID:34689324" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003996", "id": "CG-AC:RF003996", "type": "Publication", "publicationType": "Orphanet", "citation": "Cerebrotendinous xanthomatosis. Orphanet encyclopedia [Internet]", "xdbref": [ "Orphanet:909" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003997", "id": "CG-AC:RF003997", "type": "Publication", "publicationType": "GeneReview", "citation": "A Federico, GN Gallus. Cerebrotendinous xanthomatosis. 2003 Jul 16[Updated 2024 Nov 14]. In: MP Adam, S Bick, GM Mirzaa, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washingtom, Seattle; 1993-2026. ", "webUrl": "https://www.ncbi.nlm.nih.gov/books/NBK1409/", "xdbref": [ "PMID:20301583", "GeneReview:NBK1409" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003998", "id": "CG-AC:RF003998", "type": "Publication", "publicationType": "PMID", "citation": "Stelten BML, Dotti MT, Verrips A, Elibol B, Falik-Zaccai TC, Hanman K, Mignarri A, Sithole B, Steiner RD, Verma S, Yahalom G, Zubarioglu T, Mochel F, Federico A. Expert opinion on diagnosing, treating and managing patients with cerebrotendinous xanthomatosis (CTX): a modified Delphi study. Orphanet J Rare Dis. (2021) 16(1750-1172):353.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=34362411", "xdbref": [ "PMID:34362411" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF004000", "id": "CG-AC:RF004000", "type": "Publication", "publicationType": "Other", "citation": "true. Clinical evidence review of chenodeoxycholic acid for treating cerebrotendinous xanthomatosis. Nice. (2018) ", "webUrl": "https://www.england.nhs.uk/commissioning/wp-content/uploads/sites/12/2019/07/Evidence-Review-chenodeoxycholic-acid.pdf" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF004001", "id": "CG-AC:RF004001", "type": "Publication", "publicationType": "Other", "citation": "true. Clinical commissioning policy: cholic acid and chenodeoxycholic acid for treating inborn errors of bile acide synthesis. Nhs_england. (2019) ", "webUrl": "https://www.england.nhs.uk/commissioning/wp-content/uploads/sites/12/2019/07/Clinical-Commissioning-Policy_Cholic-acid-and-chenodeoxycholic-acid-for-treating-inborn-errors-of-bile-acid-sy.pdf" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF004002", "id": "CG-AC:RF004002", "type": "Publication", "publicationType": "Other", "citation": "true. Clinical evidence review of cholic acid for treating inborn errors of primary bile acid synthesis. Nice. (2018) ", "webUrl": "https://www.england.nhs.uk/commissioning/wp-content/uploads/sites/12/2019/07/Evidence-Review-cholic-acid.pdf" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF004004", "id": "CG-AC:RF004004", "type": "Publication", "publicationType": "PMID", "citation": "de Silva R, Greenfield J, Cook A, Bonney H, Vallortigara J, Hunt B, Giunti P. Guidelines on the diagnosis and management of the progressive ataxias. Orphanet J Rare Dis. (2019) 14(1750-1172):51.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=30786918", "xdbref": [ "PMID:30786918" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF004005", "id": "CG-AC:RF004005", "type": "Publication", "publicationType": "PMID", "citation": "Stelten BML, Huidekoper HH, van de Warrenburg BPC, Brilstra EH, Hollak CEM, Haak HR, Kluijtmans LAJ, Wevers RA, Verrips A. Long-term treatment effect in cerebrotendinous xanthomatosis depends on age at treatment start. Neurology. (2019) 92(1526-632X):e83-e95.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=30530799", "xdbref": [ "PMID:30530799" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF004006", "id": "CG-AC:RF004006", "type": "Publication", "publicationType": "PMID", "citation": "Zubarioglu T, Kadıoğlu-Yılmaz B, Köse E, Teke-Kısa P, Balcı MC, Yazıcı H, Özturk-Hişmi B, Akgün A, Kor D, Yıldız S, Kılıç-Yıldırım G, Soyuçen E, Akçalı A, Yıldız Y, Durmuş A, Güneş D, Soylu-Üstkoyuncu P, Kasapkara ÇS, Erdöl Ş, Göksoy E, Akar HT, Gümüş H, Ekmekçi AH, Eminoğlu FT, Arslan N, Hanağası HA, Canda E, Genç E, Özer I, Gündüz A, Kıykım E, Aktuğlu-Zeybek Ç. Long-Term Outcomes of Chenodeoxycholic Acid Therapy for Cerebrotendinous Xanthomatosis: A Nationwide Study on Prognostic Factors and Treatment Response. J Inherit Metab Dis. (2025) 48(1573-2665):e70069.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=40702717", "xdbref": [ "PMID:40702717" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF004007", "id": "CG-AC:RF004007", "type": "Publication", "publicationType": "Other", "citation": "true. Cerebrotendinous xanthomatosis. Orphananesthesia. (2017) ", "webUrl": "https://www.orphananesthesia.eu/rare-diseases/published-guidelines/cerebrotendinous-xanthomatosis/308-cerebrotendinous-xanthomatosis/file.html" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF004008", "id": "CG-AC:RF004008", "type": "Publication", "publicationType": "PMID", "citation": "Zaccai TCF, Hassin-Baer S, Kfir NC, Duell PB, Neerhof M, Sloma R, Roitman M, Kisanuki YY, Verrips A, DeBarber AE. Chenodeoxycholic acid (CDCA) treatment during pregnancy in women with cerebrotendinous xanthomatosis (CTX): Lessons learned from 19 pregnancies. Genet Med. (2024) 26(1530-0366):101086.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=38288684", "xdbref": [ "PMID:38288684" ] } ] }