UNASSIGNED: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disease associated with lipid metabolic disorders. Because of its clinical diversity and rarity, the diagnosis is often unclear. However, there is still a lack of reports on bibliometric analysis of CTX. The aim of this study was to assess the progress and research developments of CTX over the past three decades, identify emerging trends, and establish novel directions for future research.
UNASSIGNED: The eligible literature were screened from the Web of Science Core Collection (WoSCC) database. The annual publication, countries, institutions, authors, journals, keywords and references were visually analyzed by Microsoft Excel 2019, CiteSpace 6.2.R4, VOSviewer 1.6.18 and online bibliometrics website (https://bibliometric.com/).
UNASSIGNED: A total of 561 publications from WoSCC were included in this study. The United States is the country with the largest number of publications, and Karolinska Institutet is the institution with the largest number of publications. Björkhem I. ranks as the most published and cited author in the last three decades. Journal of Lipid Research is the most widely published and cited journal. The strongest burst of keywords is \"diagnosis.\"
UNASSIGNED: Unraveling the pathogenesis of CTX and improving its diagnosis and treatment continue to be critical challenges that require urgent attention. Future research endeavors will be centered on enhancing the efficiency and accuracy of early diagnosis and intervention.

There are few cerebrotendineous xanthomatosis (CTX) case series and observational studies including a significant number of Latin American patients. We describe a multicenter Brazilian cohort of patients with CTX highlighting their clinical phenotype, recurrent variants and assessing possible genotype-phenotype correlations. We analyzed data from all patients with clinical and molecular or biochemical diagnosis of CTX regularly followed at six genetics reference centers in Brazil between March 2020 and August 2023. We evaluated 38 CTX patients from 26 families, originating from 4 different geographical regions in Brazil. Genetic analysis identified 13 variants in the CYP27A1 gene within our population, including 3 variants that had not been previously described. The most frequent initial symptom of CTX in Brazil was cataract (27%), followed by xanthomas (24%), chronic diarrhea (13.5%), and developmental delay (13.5%). We observed that the median age at loss of ambulation correlates with the age of onset of neurological symptoms, with an average interval of 10 years (interquartile range 6.9 to 11 years). This study represents the largest CTX case series ever reported in South America. We describe phenotypic characteristics and report three new pathogenic or likely pathogenic variants.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX, OMIM #213700) is a rare inherited metabolic disease caused by the mutation in the CYP27A1 gene. Spinal CTX is a rare clinical subgroup of CTX which lacks typical symptoms seen in classical CTX. Here we report a spinal CTX case revealed double mutation of CYP27A1 gene.
METHODS: A 42-year-old Asian man visited our hospital with spastic gait started at 35. Physical examination showed bilateral masses on his Achilles tendons and were identified as xanthoma on ankle magnetic resonance imaging (MRI). Brain and spinal cord MRI revealed high signal lesions in bilateral cerebellar dentate nuclei and long tract lesions involving lateral corticospinal and gracile tracts. Gene analysis revealed double heterozygous mutation, c.223C > T (p. Gln75Ter) and c.1214G > A (p. Arg405Gln).
CONCLUSIONS: We believe that novel mutation detected in our case might have a role in the pathomechanism in CTX. Moreover, spinal CTX should be considered in the patients only presenting with pyramidal symptoms, as CTX shows good prognosis in early treatment with chenodeoxycholic acid.

Xanthomatosis is a genetic disease inherited in an autosomal recessive manner. The specific phenotypic features are associated with patient\'s genetic profile. The result of the mutation is disorder of cholesterol synthesis and the accumulation of its precursors in tissues. The characteristic symptoms are progressive cerebellar ataxia, cataract, diarrhea, and the deposition of cholesterol in the tendons. Our objective is to follow-up information to treatment efficacy of 22-year-old patient diagnosed with cerebrotendinous xanthomatosis through 1.5 year observation. In 2012, an 11-year-old patient with a long history of deformed feet and frequent yellowing of the skin, was admitted to the Department of Neurology due to seizures. In 2013, the patient began to suffer from diarrhea, and its frequency was correlated with the concentration of bilirubin in the blood. In the same year cataract was diagnosed. Gradually, the patient starts to complain about progressive difficulties in moving. In 2019, genetic tests confirmed the diagnosis of cerebrotendinous xanthomatosis. Since July 2021, the patient has been treated with chenodeoxycholic acid. The deterioration of patient\'s mobility has been significantly inhibited, consequently his quality of life has improved. The presented case report underscores the efficacy of CDCA supplementation in halting the progression of CTX, resulting in marked improvements in the patient\'s quality of life.

Cerebrotendinous xanthomatosis (CTX) is a rare inherited metabolic disease attributed to the mutation of the gene CYP27A1, resulting in sterol 27-hydroxylase deficiency characterized by deposition of cholestanol and cholesterol in several tissues, like the central nervous system and tendons. Furthermore, cataracts, gallstones, diarrhea and premature atherosclerosis have been reported. Nonetheless, clinical development is extremely heterogeneous in CTX. We report here two cases of CTX genetic alteration in the absence of cholestanol elevation in plasma and tendons but with prominent xanthomas. We propose that CTX may not be characteized by increased plasma cholestanol concentration due to alteration in the sterol 27-hydroxylase gene, but is a more complex pathology where there is significant genetic heterogeneity caused by various CYP27A1 mutations.

Cerebrotendinous xanthomatosis is a rare and treatable metabolic disorder related to the accumulation of cholestanol. This disorder is primarily associated with motor and cognitive impairments, although the latter has not been extensively characterized. The objectives of this work were to define the cognitive profile found in cerebrotendinous xanthomatosis patients, investigate the progression of cognitive impairment over time, and search for radio-clinical correlations. Through a multicentric chart review study, we collected cognitive and radiological data from nine children and eighteen adults with genetically proven cerebrotendinous xanthomatosis. We performed a volumetric and morphological analysis of the brain magnetic resonance imaging. In our cohort, 44% (4/9) of children and 78% (14/18) of adults exhibited cognitive impairment that can be severe. The study revealed a significant impairment in various cognitive domains, specifically executive, attentional, language, and visuo-spatial. Among adults, 16% (3/18) developed dementia after age 50. These three patients had delayed chenodeoxycholic acid treatment and important cerebral atrophy. Besides these three cases of late-onset cognitive decline, Mini-Mental State Evaluation was generally stable, suggesting cognitive impairment due to a neurodevelopmental disorder and persisting in adulthood. Cognitive impairment was less common in children, possibly related to early chenodeoxycholic acid treatment in our cohort. The severity of magnetic resonance imaging abnormalities did not predict cognitive impairment in patients. Overall, in cerebrotendinous xanthomatosis, cognitive impairment can be severe and mainly neurodevelopmental. Early chenodeoxycholic acid treatment might be associated with a reduced risk of cognitive decline.

OBJECTIVE: Cerebrotendinous xanthomatosis (CTX) is an inherited metabolic disorder characterized by progressive neurologic and extraneurologic findings. The aim of this retrospective, descriptive study was to explore the time of presentation and diagnosis, and to expand the phenotype and genotype of CTX, based on a nationwide and comprehensive series of patients in Turkey.
METHODS: The demographic, clinical, biochemical and genotypic characteristics of the CTX patients were reviewed. Data on molecular analysis, age of onset and diagnosis, diagnostic delay, neurologic and extraneurologic symptomatology, results of plasma cholestanol levels, brain magnetic resonance imaging and electromyography at the time of diagnosis were reviewed.
RESULTS: 100 confirmed CTX patients from 72 families were included. The mean age at diagnosis was 28.16 ± 14.28 years, and diagnostic delay was 18.39 ± 13.71 years. 36 patients were diagnosed in childhood. Frequency of intention tremor (p = 0.069), peripheral neuropathy (p = 0.234) and psychiatric manifestations (p = 0.396) did not differ between two groups, demonstrating the high rate in pediatric patients. Three adult patients showed a milder phenotype without neurologic involvement. Seven patients had normal plasma cholestanol levels despite neurological impairment. Sequencing of the CYP27A1 gene revealed 25 different variants, with a novel c.671_672del variant not previously described in literature.
CONCLUSIONS: Based on the observations of this Turkish CTX cohort, it is emphasized that the true prevalence of CTX is probably underestimated and that it has a wide spectrum of clinical phenotypes even without neurological impairment. In children, abnormal cerebellar findings, peripheral neuropathy and psychiatric findings associated with intellectual disability have been suggested as warning signs to avoid diagnostic delay. In cases of clinical suspicion, molecular analysis is recommended despite normal plasma cholestanol levels, as severe neurologic involvement may occur in CTX patients without elevated cholestanol levels.

UNASSIGNED: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder caused by bi-allelic pathogenic variants in CYP27A1 gene that results in the deposition of cholestanol in the eyes, tendons, soft tissues and nervous system leading to cataracts, xanthomas, and various neuropsychiatric manifestations. The aim of our study is to describe the clinical, radiological and genetic profile of patients with CTX.
UNASSIGNED: This is a retrospective chart review of patients with CTX diagnosed based on classical clinical and radiological findings. The available clinical details, and investigations, including imaging, electrophysiological, pathological and genetic data, were documented.
UNASSIGNED: Five patients (4 males) were recruited in the study. The median age at presentation was 32 years (range: 21-66 years). Walking difficulty was the most common symptom at presentation. All patients had cataracts, tendon xanthomas, eye movement abnormalities, dysarthria, pyramidal signs, ataxia and gait abnormality. Dystonia was noted in three patients. Palatal tremor and parkinsonism were noted in one patient each. In MRI brain, dentate, and corticospinal tract involvement were the most frequent imaging findings. Bilateral hypertrophic olivary degeneration was noted in one patient and hot cross bun sign in two. Three patients underwent genetic testing and all had pathogenic variants confirming the diagnosis.
UNASSIGNED: CTX is a rare treatable disorder. Apart from the usual neurological presentation with spastic-ataxia, it can present at a later age with parkinsonism. Typical patterns of imaging findings are helpful in early diagnosis which aids in the treatment to prevent the neurological sequelae of the disease.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX, OMIM #213700) is a rare but treatable lipid storage disease resulting from mutations in the CYP27A1 gene.
OBJECTIVE: The study aims to evaluate patients diagnosed with CTX and reveal new information, especially about the signs of CTX and patients\' response to the treatment.
METHODS: The study was conducted retrospectively in 12 definitively diagnosed CTX patients. The patients\' clinical, laboratory, imaging, genetic findings, and chenodeoxycholic acid (CDCA) treatment results were analyzed.
RESULTS: The median age at diagnosis for the patients was 16.5 years (minimum-maximum: 7-32). Juvenile cataracts, detected in more than 90% (11/12) of the patients, were the most common clinical finding. Malar rash, not previously reported in the literature for CTX, was present in 75% (9/12) of the patients. Hand tremors, the first neurological symptom, occurred in adolescence and were the initial symptom of the disease in five patients. Hand tremors were present in 83.3% (10/12) of the patients. Hand tremors (in 5 patients) and malar rash (in 2 patients) were clinical findings with full recovery due to the CDCA treatment.
CONCLUSIONS: The study defines the malar rash finding, which has not been reported in the literature before, as a possible new clinical finding in CTX disease, attributed to its partial or full recovery with CDCA treatment. Additionally, as a novelty in the literature, our study highlights the full recovery of neurological findings, such as hand tremors, in CTX. Patients presenting with hand tremors and malar rash, especially in adolescence, should undergo CTX investigation for early diagnosis and treatment.

BACKGROUND: Cerebrotendinous Xanthomatosis (CTX) is a rare autosomal recessive lipid storage disorder caused by loss of function variants in the CYP27A1 gene which encodes sterol 27-hydroxylase, on chromosome 2q35. Although the symptoms begin commonly in infancy, CTX diagnosis is often delayed. The aim of this study is to review the orthopedic findings of the disease by providing an overview of the clinical features of the disease. It is to raise awareness of this condition for which early diagnosis and treatment are important.
METHODS: We retrospectively evaluated the clinical, laboratory, radiological, and genetic findings of eight patients from four families who were admitted to our Orthopedics and Traumatology Department between 2017 and 2022 due to bilateral Achilles tendon xanthomas, were found to have high cholestanol and CYP27A1 gene mutations.
RESULTS: The mean age of patients was 37, and five of them were male. The mean age at the onset of symptoms was 9.25 years. The mean age of initial diagnosis was 33.75 years. Between symptom onset and clinical diagnosis, an average delay of 24.5 years was observed. All patients had bilateral Achilles tendon xanthoma. Notably, a novel variant (c.670_671delAA) in CYP27A1 gene was identified in three patients who also presented with peripheral neuropathy and bilateral pes cavus. One patient had osteoporosis and four patients had osteopenia. Five patients had a history of bilateral cataracts. Furthermore, three of the patients had early-onset chronic diarrhea and three of the patients had ataxia. Two of the patients had epilepsy and seven of the patients had behavior-personality disorder. All patients had low intelligence, but none of them had cardiac disease.
CONCLUSIONS: We present the diagnostic process and clinical features which the largest CTX case series ever reported from single orthopedic clinic. We suggest that patients with normal cholesterol levels presenting with xanthoma being genetically analyzed by testing at their serum cholestanol level, and that all siblings of patients diagnosed with CTX be examined.