Cerebrotendinous xanthomatosis: The diagnostic challenge

Jaramillo Toro, Carolina; Baquero Marín, Pedro José; Bados Enríquez, Diego Mauricio

doi:10.1016/j.medcle.2018.05.049

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This abnormality promotes the development of cholestanol deposits in various body tissues, such as brain, tendons and lens. Its diagnosis is based on the identification of high serum cholestanol levels, of urinary bile alcohols and low bile chenodeoxycholic acid levels.<a class="elsevierStyleCrossRef" href="#bib0030">1</a> In Colombia, only one clinical report is available on the neurological manifestations caused by CTX.<a class="elsevierStyleCrossRef" href="#bib0035">2</a> Mental disorders such as personality changes associated with irritability, depression, frank psychosis and suicidal ideation are poorly reported in the first diagnosis.<a class="elsevierStyleCrossRef" href="#bib0040">3</a> Therefore, we will describe a case report that allows us to visualize the importance of a comprehensive approach for this type of patients. This case report is on a 49-year-old Colombian man with a university education who had been diagnosed with CTX through his cardinal symptoms (mainly Achilles tendon xanthomas, bilateral cataracts and neurological compromise). For the diagnosis, we considered the serum cholestanol levels, being 12.5μmol/l (diagnostic value: 330±30mg/dl), which initially ruled out one of the CTX diagnostic methods. Therefore, we chose a DNA microarray study under the Affymetrix CytoScan® HD platform, reporting the presence of 19 regions with loss of heterozygosity, in addition to significant lengths 56,000–10,000kbp in chromosome 2 region q35–q37, which would indicate a compromise in the CTX gene.The patient attended a psychiatric assessment where he reported predominant “affective” symptoms, such as low mood, sadness, anhedonia, insomnia and altered sleep–wake cycles, recurrent thoughts of death without an elaborated suicidal ideation, ideas of disability, hopelessness with a negative vision of himself, future and environment, anguish and uncertainty on the development and prognosis of his disease and “cognitive”, these being basically a lower capability to concentrate and retain new information. These symptoms were reported at his admission with a neuropsychological diagnosis of mild cognitive impairment.Likewise, psychotic symptoms were identified such as simple auditory hallucinations and constant fear. He was first treated with serotonin reuptake inhibitors and trazodone, and he underwent occupational therapy throughout his hospital stay, with persistent ideas of disability, which were counteracted with sertraline, clonazepam and trazodone.In a neuropsychiatric level he showed anxiety exacerbation with symptoms of dromomania and generalized tremor syndrome, with disorientation in person, time and place, and reoccurrence of psychotic symptoms, with more elaborate hallucinations. Additionally, the patient presented episodes of dissociation going to unknown places (other municipalities).The patient underwent an electroencephalogram, whose results were normal. In this admission, unlike the first, the predominant symptom is severe, refractory anxiety, after one month of therapy with sertraline, clonazepam and quetiapine. However, the depressive and anxious symptoms decrease and psychiatric assessment is indicated for the onset of cognitive/behavioral therapy.Taking into account the reported cardinal symptoms, we approached the attached symptoms of affective and anxious predominance. To this purpose, the patient underwent 4 neuropsychiatric tests: the Montreal cognitive assessment scale (MoCA), the obsessive compulsive disorder (OCD) test and the Hamilton Depression Rating Scale for his depression and anxiety whose results are listed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<a class="elsevierStyleCrossRef" href="#bib0030">1</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>In the CTX, the most frequent conditions in the scientific literature are neurological.<a class="elsevierStyleCrossRef" href="#bib0045">4</a> Several cases of patients with associated psychiatric disorders such as those described in our patient have been reported. However, the clinical report of patients with these characteristics is unfortunately quite frequent.<a class="elsevierStyleCrossRef" href="#bib0050">5</a> However, we must bear in mind that these patients benefit from a comprehensive treatment that includes chenodeoxycholic acid to improve their neurological disorders. And also the support of a psychiatric treatment team helps to provide a better quality of life." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Jaramillo Toro C, Baquero Marín PJ, Bados Enríquez DM. Xantomatosis cerebrotendinosa: el desafío diagnóstico. Med Clin (Barc). 2019;152:123–124." ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "This study has been presented at the International Conference on Rare Diseases (CCIER), 2016, Cali, Colombia, and at the Colombian Student's Congress of Medical Research (CECIM), 2017, Boyacá, Colombia." ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Psychiatric test \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Result \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Yale-Brown obsessive-compulsive scale in Spanish \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Anxiety caused by symmetry OCD \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hamilton Rating Scale for depression \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Score 14–18 moderate depression \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hamilton Rating Scale for anxiety \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Psychological anxiety \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Montreal Cognitive Assessment Scale \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mild cognitive impairment \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1949184.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Results of psychiatric tests." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cerebrotendinous xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Nie" 1 => "G. Chen" 2 => "X. Cao" 3 => "Y. Zhang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13023-014-0179-4" "Revista" => array:5 [ "tituloSerie" => "Orphanet J Rare Dis" "fecha" => "2014" "volumen" => "9" "paginaInicial" => "179" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25424010" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Novel cerebrotendinous xanthomatosis mutation causes familial early dementia in Colombia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Giraldo-Chica" 1 => "N. Acosta-Baena" 2 => "F. Lopera" 3 => "N. Pineda" 4 => "L. Urbano" 5 => "L. Velilla" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Biomedica" "fecha" => "2015" "volumen" => "3535" "paginaInicial" => "563" "paginaFinal" => "571" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Psychiatric manifestations in cerebrotendinous xanthomatosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M. 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Hassin-Baer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/WNF.0b013e318288076a" "Revista" => array:7 [ "tituloSerie" => "Clin Neuropharmacol" "fecha" => "2013" "volumen" => "36" "paginaInicial" => "78" "paginaFinal" => "83" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23673909" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0005791611000991" "estado" => "S300" "issn" => "00057916" ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Trastornos psiquiátricos secundarios a enfermedades neurometabólicas" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P.M. Herrera" 1 => "A. Vélez Van Meerbeke" 2 => "O. 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Vol. 152. Issue 3.

Pages 123-124 (February 2019)

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